bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of Cognitive Processes
Authors: Monsell Stephen , Driver Jon
Published: May 2020

The thirty-two contributions discuss evidence from psychological experiments with healthy and brain-damaged subjects, functional imaging, electrophysiology, and computational modeling.

One of the most challenging problems facing cognitive psychology and cognitive neuroscience is to explain how mental processes are voluntarily controlled, allowing the computational resources of the brain to be selected flexibly and deployed to achieve changing goals. The eighteenth of the celebrated international symposia on Attention and Performance focused on this problem, seeking to banish or at least deconstruct the "homunculus": that conveniently intelligent, but opaque, agent still lurking within many theories, under the guise of a central executive or supervisory attentional system assumed to direct processes that are not "automatic."

The thirty-two contributions discuss evidence from psychological experiments with healthy and brain-damaged subjects, functional imaging, electrophysiology, and computational modeling. Four sections focus on specific forms of control: of visual attention, of perception-action coupling, of task-switching and dual-task performance, and of multistep tasks. The other three sections extend the interdisciplinary approach, with chapters on the neural substrate of control, studies of control disorders, and computational simulations. The progress achieved in fractionating, localizing, and modeling control functions, and in understanding the interaction between stimulus-driven and voluntary control, takes research on control in the mind/brain to a new level of sophistication.

Bradford Books imprint
The Closed World
Authors: Edwards Paul N.
Published: May 2020

The Closed World offers a radically new alternative to the canonical histories of computers and cognitive science. Arguing that we can make sense of computers as tools only when we simultaneously grasp their roles as metaphors and political icons, Paul Edwards shows how Cold War social and cultural contexts shaped emerging computer technology—and were transformed, in turn, by information machines.

The Closed World explores three apparently disparate histories—the history of American global power, the history of computing machines, and the history of subjectivity in science and culture—through the lens of the American political imagination. In the process, it reveals intimate links between the military projects of the Cold War, the evolution of digital computers, and the origins of cybernetics, cognitive psychology, and artificial intelligence.

Edwards begins by describing the emergence of a "closed-world discourse" of global surveillance and control through high-technology military power. The Cold War political goal of "containment" led to the SAGE continental air defense system, Rand Corporation studies of nuclear strategy, and the advanced technologies of the Vietnam War. These and other centralized, computerized military command and control projects—for containing world-scale conflicts—helped closed-world discourse dominate Cold War political decisions. Their apotheosis was the Reagan-era plan for a "Star Wars" space-based ballistic missile defense.

Edwards then shows how these military projects helped computers become axial metaphors in psychological theory. Analyzing the Macy Conferences on cybernetics, the Harvard Psycho-Acoustic Laboratory, and the early history of artificial intelligence, he describes the formation of a "cyborg discourse." By constructing both human minds and artificial intelligences as information machines, cyborg discourse assisted in integrating people into the hyper-complex technological systems of the closed world.

Finally, Edwards explores the cyborg as political identity in science fiction—from the disembodied, panoptic AI of 2001: A Space Odyssey, to the mechanical robots of Star Wars and the engineered biological androids of Blade Runner—where Information Age culture and subjectivity were both reflected and constructed.

Inside Technology series
Developmental Psychobiology
Authors: Michel George F. , Moore Celia L.
Published: May 2020

This text is the first to provide a coherent theoretical treatment of the flourishing new field of developmental psychobiology which has arisen in recent years on the crest of exciting advances in evolutionary biology, developmental neuroscience, and dynamic systems theory.

Michel and Moore, two of the field's key pioneers and researchers, integrate primary source information from research in both biological and psychological disciplines in a clear account of the frontier of biopsychological investigation and theorizing.

Explicitly conceptual and historical, the first three chapters set the stage for a clear understanding of the field and its research, with particular attention to the nature-nurture question. The next three chapters each provide information about a basic subfield in biology (genetics, evolution, embryology) that is particularly relevant for developmental studies of behavior. These are followed by extended treatments of three spheres of inquiry (behavioral embryology, cognitive neuroscience, animal behavior) in terms of how a successful interdisciplinary approach to behavioral development might look. A final chapter comments on some of the unique aspects of development study.

From this detailed and clearly organized text, students will achieve a firm grasp of some of science's most fertile questions about the relation between evolution and development, the relation between brain and cognitive development, the value of a natural history approach to animal behavior—and what it teaches us about humans—and much more. Each chapter contains material that questions the conventional wisdom held in many subdisciplines of biology and psychology. Throughout, the text challenges students to think creatively as it thoroughly grounds them in the field's approach to such topics as behavioral-genetic analysis, the concept of innateness, molecular genetics and development, neuroembryology, behavioral embryology, maturation, cognition, and ethology.

Bradford Books imprint
The Nature of Cognition
Authors: Allen Rhianon , Buchner Axel , Ceci Stephen , Cole Michael , Debruyn Eduardus H. , dunne Randall , Frensch Peter , Grigorenko Elena L. , Hunt Earl , Johnson-Laird Philip , Kahana Michael J. , Kihlstrom John F. , Loftus Geoffrey , Makin Valerie , McNamara Timothy , Nelson Thomas , Nickerson Raymond S. , Oransky Natalie , Phelps Elizabeth A. , Proffitt Dennis R. , Reber Arthur , Reber Paul J. , Robinson Daniel N. , Rosenblum Tina B. , Ross Brian , Sloman Steven A. , Carpenter Patricia
Published: May 2020

Most cognitive psychology texts are organized around empirical findings on standard substantive topics such as perception, memory, vision, and language. This book is the first to introduce the study of cognition in terms of the major conceptual themes that underlie virtually all the substantive topics. Taking a dialectical approach, the chapters contrast alternative approaches to the underlying themes (e.g., domain-generality vs. domain-specificity), then show how a synthesis of the two approaches provides the best understanding. The book is organized into six sections: general issues in cognition, representation and process in cognition, methodology in cognition, kinds of cognition, group and individual differences in cognition, and a conclusion.

Contributors

Rhianon Allen, Axel Buchner, Patricia A. Carpenter, Stephen J. Ceci, Michael Cole, Eduardus DeBruyn, Randall W. Engle, Peter A. Frensch, Elena L. Grigorenko, Earl Hunt, P.N. Johnson-Laird, Marcel Adam Just, Michael Kahana, John F. Kihlstrom, Geoffrey Loftus, Valerie S. Makin, Timothy P. McNamara, Thomas O. Nelson, Raymond S. Nickerson, Natalie Oransky, Elizabeth A. Phelps, Dennis R. Proffitt, Arthur S. Reber, Paul J. Reber, Daniel N. Robinson, Tina B. Rosenblum, Brian H. Ross, Steven Sloman, Robert J. Sternberg

Bradford Books imprint
On the Origin of Objects
Authors: Smith Brian Cantwell
Published: May 2020

On the Origin of Objects is the culmination of Brian Cantwell Smith's decade-long investigation into the philosophical and metaphysical foundations of computation, artificial intelligence, and cognitive science. Based on a sustained critique of the formal tradition that underlies the reigning views, he presents an argument for an embedded, participatory, "irreductionist," metaphysical alternative. Smith seeks nothing less than to revise our understanding not only of the machines we build but also of the world with which they interact.

On the Origin of Objects is the culmination of Brian Cantwell Smith's decade-long investigation into the philosophical and metaphysical foundations of computation, artificial intelligence, and cognitive science. Based on a sustained critique of the formal tradition that underlies the reigning views, he presents an argument for an embedded, participatory, "irreductionist," metaphysical alternative. Smith seeks nothing less than to revise our understanding not only of the machines we build but also of the world with which they interact.

Smith's ambitious project begins as a search for a comprehensive theory of computation, able to do empirical justice to practice and conceptual justice to the computational theory of mind. A rigorous commitment to these two criteria ultimately leads him to recommend a radical overhaul of our traditional conception of metaphysics.

Everything that exists—objects, properties, life, practice—lies Smith claims in the "middle distance," an intermediate realm of partial engagement with and partial separation from, the enveloping world. Patterns of separation and engagement are taken to underlie a single notion unifying representation and ontology: that of subjects' "registration" of the world around them.

Along the way, Smith offers many fascinating ideas: the distinction between particularity and individuality, the methodological notion of an "inscription error," an argument that there are no individuals within physics, various deconstructions of the type-instance distinction, an analysis of formality as overly disconnected ("discreteness run amok"), a conception of the boundaries of objects as properties of unruly interactions between objects and subjects, an argument for the theoretical centrality of reference preservation, and a theatrical, acrobatic metaphor for the contortions involved in the preservation of reference and resultant stabilization of objects. Sidebars and diagrams throughout the book help clarify and guide Smith's highly original and compelling argument.

Bradford Books imprint
Protocol Analysis
Authors: Ericsson K. Anders , Simon Herbert A.
Published: May 2020

Since the publication of Ericsson and Simon's ground-breaking work in the early 1980s, verbal data has been used increasingly to study cognitive processes in many areas of psychology, and concurrent and retrospective verbal reports are now generally accepted as important sources of data on subjects' cognitive processes in specific tasks. In this revised edition of the book that first put protocol analysis on firm theoretical ground, the authors review major advances in verbal reports over the past decade, including new evidence on how giving verbal reports affects subjects' cognitive processes, and on the validity and completeness of such reports.

In a substantial new preface Ericsson and Simon summarize the central issues covered in the book and provide an updated version of their information-processing model, which explains verbalization and verbal reports. They describe new studies on the effects of verbalization, interpreting the results of these studies and showing how their theory can be extended to account for them. Next, they address the issue of completeness of verbally reported information, reviewing the new evidence in three particularly active task domains. They conclude by citing recent contributions to the techniques for encoding protocols, raising general issues, and proposing directions for future research.

All references and indexes have been updated.

Bradford Books imprint
Teaching Accessibility in Computer Science and Related Disciplines
Authors: Lewthwaite Sarah , Coverdale Andy , Butler-Rees Angharad
Published: May 2020

Background: Imperatives for digital inclusion mean there is growing demand for graduates with the knowledge and skills to produce digital services that are accessible to disabled people and older populations. Accessibility is mandated by a body of laws that constitute digital disability rights, and internet use among disabled people is increasing (ONS, 2019). However, a lack of progress in the delivery of accessible mobile web-based services, tools and resources mean disabled and older people face persistent digital barriers. There is a pressing need to develop accessibility capacity in the digital workforce. To this end, this systematic literature review seeks to establish what is empirically known about the effective teaching and learning of digital accessibility through the lens of pedagogy.
Methods/Design: The review will consider research (1999-2019) which focuses on the teaching and learning of digital accessibility in higher education and the workplace. The focus is on how pedagogy is enacted - the pedagogic practice of teaching - rather than curriculum development or other activities that relate to planning or governance. Two databases will be searched, using identified keywords. To identify further papers, backward- and forward- citation analysis is used. Researchers will work iteratively with the data, to ensure no loss of context through data extraction. A narrative synthesis of the findings will be presented.
Discussion: The review will collate literature on the pedagogy of accessibility education, reporting on how the teaching or learning of digital accessibility is effectively undertaken. It will identify the empirical basis for accessibility pedagogy.
Comparative Eriksonian Psychocritical Analysis of Miss Cora by Julio Cortázar, and The Lame Pigeon by Eduardo Mendicutti
Authors: Sevilla Vallejo Santiago
Published: May 2020

In the adolescence, it takes places identity exploration, in which the fundamentals that define the way the individual thinks, feels and acts would be established; or identity confusion, a defined imagine of the mentioned aspects wouldn’t be reached. In this research, we compare Miss Cora by Julio Cortázar and The Lame Pigeon by Eduardo Mendicutti, whose protagonists are two boys who are at the beginning of adolescence and they have other characteristics that set a similar starting point. Both protagonists are discovering a new manner of thinking and feeling and they have their first experience of sexual desire. However, their experiences are hard because their families and the environment that surrounds them don’t accept the change in which they are immersed and both of them suffer to forge an own identity. Miss Cora and The Lame Pigeon reflect the fragility of the construction of the adolescence identity.
Turkish Teachers’ Assessment Situations: A Study on Exam Papers
Authors: Akçay Ahmet , Tunagür Muhammed , Karabulut Ahmet
Published: May 2020

This study aims to examine Turkish exam papers of the students, who study in the secondary school of 5th, 6th, 7th and 8th classes. The exam papers have been examined from various aspects, including the number and type of questions, the language expression and distribution of the questions, the cognitive level (according to the Bloom’s taxonomy), the type of texts used, and the visuals use. The samples of the study were selected using convenience sampling method from 17 secondary schools located in the center of Ağrı Province in Turkey and the exam papers prepared by 36 Turkish teachers who worked at these schools. The tests which were examined included 2633 questions in 161 exam papers. We also developed “the Exam Paper Examination Form” for collecting more data which we analyzed and interpreted by using the document analysis model. According to the results obtained, it has been found that the teachers mostly prefer to use the multiple-choice question type in the Turkish exam papers; the questions are mostly related to grammar and reading; the teachers do not prefer to ask questions on speaking and listening; and except for spelling errors no deficiency is detected in the language of the exam papers. In addition, according to Bloom’s taxonomy, the questions are mostly at the comprehension level whereas questions related to the analyzing, evaluating and creating levels that require high level thinking skills are rarely used. Based on the results, suggestions have been presented for Turkish teachers to prepare exams.
Second Language Speaking Anxiety Among Malaysian Postgraduate Students at a Faculty of Education
Authors: Badrasawi Kamal J I , Solihu Abdulateef , Tunku Ahmad Tunku Badariah
Published: May 2020

This study examined the level of L2 speaking anxiety among school teachers undertaking a master’s degree at the International Islamic University Malaysia and sought to determine if the anxiety level would differ by gender, school location and teaching subject. A convenience sample of 290 teachers completed a 12-item survey on L2 speaking anxiety adapted from Nazir et al. (2014). The survey data were analyzed using the Rasch measurement modeling for polytomous data, independent samples t-test and one-way ANOVA. Overall, the respondents did not show high levels of speaking anxiety, [Mean -.89 logits]. Most were largely worried about being able to express themselves effectively in English [-.66 logits], making mistakes in speaking [-.31 logits], and how lecturers would react to their mistakes [-.38 logits]. The sample’s speaking anxiety scores were found to differ significantly by teaching subject, while no statistically significant differences were observed in regard to gender and school location. The results imply that the teachers need to be helped in terms of confronting the factors that cause them to be anxious about speaking in English. In terms of research, in-depth qualitative studies need to be undertaken to further understand the nature of L2 speaking anxiety among schoolteachers, while quantitative studies with larger samples are recommended to uncover underlying factors of speaking anxiety.
The Impact of Visual Literacy Awareness Education on Verbal and Writing Skills of Middle School Students
Authors: Kaya Mustafa
Published: May 2020

The most important source for the acquisition of the skills targeted in Turkish language course is the texts included in the textbooks. However, recent advances in computers have allowed the visual elements to be included in the education system in addition to textual elements. Visual elements are used in several media, especially in television and the Internet as well as books, magazines, newspapers, etc. For the acquisition of visual reading and visual reading skills, visual reading education is of great importance. In the present study that investigated the effect of visual reading education and visual elements on writing and verbal skills of middle school students, pretest-posttest random sampling design with control group, an experimental design was used. The study researcher randomly assigned 17 students in the study group and 18 students in the control group who were attending the 5th grade in Ahmet Yesevi ISE Middle School during the 2018-2019 academic year. The Written Expression Evaluation Scale (WEES) and Effective Speech Skills in Turkish Language Scale (VRSTLS) were used as data collection instruments. The study data were analyzed with parametric independent and paired samples t-tests. SPSS-PASW Statistics (Version 22) was used in analyses. The study findings demonstrated that visual reading awareness education had a significant impact on the development of writing and verbal skills of the students.
Psychosocial and occupational factors associated with low back pain among nurses in Saudi Arabia
Authors: Jradi Hoda , Alanazi Hajjah , Mohammad Yousef
Published: May 2020

Introduction

Low back pain (LBP) is a major health problem with significant public health and economic burden. Few studies have clarified the role of psychosocial factors in LBP occurrence. In this study, we assessed psychosocial and occupational factors associated with LBP, within the last 12 months, among nurses in Saudi Arabia.

Methods

A cross-sectional study was conducted in 16 hospitals across Riyadh, Saudi Arabia. A sample of 427 nurses was surveyed. The anonymous questionnaire contained valid and reliable questions assessing LBP, as pain between the costal margins of the 12th rib and the gluteal folds, and questions related to psychosocial and work-related factors experienced by the nurses. Descriptive statistics were reported for all variables. Univariate and multivariate logistic regression analyses assessed the likelihood of significant associations between study variables and LBP.

Results

The prevalence of reported LBP was 80%. Factors associated with LBP in univariate analysis were frequent lifting (OR = 2.32; 95%CI: 1.34-4.01), work-related stress (OR = 5.81; 95%CI: 3,37-9,62), lack of job satisfaction (OR = 2.08; 95%CI: 1.13-3.85), work-related problems (OR = 2.40; 95%CI: 1.44-4.02), and financial problems (OR = 2.08; 95%CI: 1.26-3.38), while factors that remained significantly associated with LBP in the final multivariate analyses were frequent lifting (OR = 2.04; 95%CI:1.09-3.81), work-related stress (OR = 4.22; 95%CI: 2.34-7.48), and lack of job satisfaction (OR = 1.87; 95%CI: 1.24-3.58).

Conclusion

The prevalence of LBP is high in this sector of the health-care workforce. Ergonomic and psychosocial factors may be considered contributing factors for low back pain. Special attention to stress-reduction, counseling, and policies to improve job satisfaction are recommended in order reduce LBP and improve the health and safety of nurses in Saudi Arabia.
Targeting RIPK3 oligomerization blocks necroptosis without inducing apoptosis
Authors: Li Wenjuan , Ni Hengxiao , Wu Shaofeng , Han Shang , Chen Chang'an , Li Li , Li Yunzhan , Gui Fu , Han Jiahuai , Deng Xianming
Published: May 2020

Receptor‐interacting serine/threonine‐protein kinase 3 (RIPK3) is a central protein in necroptosis with great potential as a target for treating necroptosis‐associated diseases, such as Crohn's disease. However, blockade of RIPK3 kinase activity leads to unexpected RIPK3‐initiated apoptosis. Herein, we found that PP2, a known SRC inhibitor, inhibits TNF‐α‐induced necroptosis without initiating apoptosis. Further investigation showed that PP2 acts as an inhibitor of not only SRC but also RIPK3. PP2 does not disturb the integrity of the RIPK1–RIPK3–mixed lineage kinase domain‐like pseudokinase (MLKL) necroptosome or the autophosphorylation of RIPK3 at T231/S232 but disrupts RIPK3 oligomerization, thereby impairing the phosphorylation and oligomerization of MLKL. These results demonstrate the essential role of RIPK3 oligomerization in necroptosis and suggest a potential RIPK3 oligomerization‐targeting strategy for therapeutic development.
The ambivalent role of water at the origins of life
Authors: do Nascimento Vieira Andrey , Kleinermanns Karl , Martin William F. , Preiner Martina
Published: May 2020

Life as we know it would not exist without water. However, water molecules not only serve as a solvent and reactant but can also promote hydrolysis, which counteracts the formation of essential organic molecules. This conundrum constitutes one of the central issues in origin of life. Hydrolysis is an important part of energy metabolism for all living organisms but only because, inside cells, it is a controlled reaction. How could hydrolysis have been regulated under prebiotic settings? Lower water activities possibly provide an answer: geochemical sites with less free and more bound water can supply the necessary conditions for protometabolic reactions. Such conditions occur in serpentinising systems, hydrothermal sites that synthesise hydrogen gas via rock–water interactions. Here, we summarise the parallels between biotic and abiotic means of controlling hydrolysis in order to narrow the gap between biochemical and geochemical reactions and briefly outline how hydrolysis could even have played a constructive role at the origin of molecular self‐organisation.
BNIP3 contributes to cisplatin‐induced apoptosis in ovarian cancer cells
Authors: Jia Jinghui , Yang Xiaoxin , Zhao Qing , Ying Feiquan , Cai E , Sun Si , He Xiaoqi
Published: May 2020

BNIP3 is a proapoptotic protein that mediates apoptosis, necrosis and autophagy. However, the involvement of BNIP3 in cisplatin‐induced apoptosis in ovarian cancer is not clear. In this study, we examined the role of BNIP3 in ovarian cancer during cisplatin treatment and its correlation with clinical outcomes. We first measured cisplatin cytotoxicity and BNIP3 levels before and after cisplatin exposure for ovarian cancer cell lines A2780, SKOV3, OVCAR4, OV2008, ES2 and HO8910. BNIP3 was observed to be differentially expressed in these cell lines, and cisplatin induced a significant increase in BNIP3 levels in A2780 and OVCAR4. BNIP3 knockdown with siRNA in A2780 and OVCAR4 significantly reduced cisplatin cytotoxicity in these two cell lines and alleviated cisplatin‐induced apoptosis. We searched the online databases Gene Expression Omnibus and The Cancer Genome Atlas to analyze the correlation between BNIP3 level and overall survival and progression‐free survival in patients with ovarian cancer. Pooled analyses showed that higher BNIP3 level was correlated with poorer overall survival (95% confidence intervals; hazard ratio = 1.18, 1.04–1.34;P = 0.013) and progression‐free survival (95% confidence intervals; hazard ratio = 1.26, 1.10–1.43;P = 0.00049). However, the results of individual datasets and stratification analyses of histology, FIGO (Federation Internationale de Gynecolgie et d’Obstetrique) stage, chemotherapy regimen and P53 mutation status varied. These findings indicate that cisplatin‐induced apoptosis is dependent on BNIP3 level in ovarian cancer cell lines. Targeting BNIP3 may therefore be a potential way of restoring cisplatin sensitivity.
Peptide Neurotransmitters and Hormones
Authors: Gonzalez‐Lozano Miguel A , Li Ka Wan
Published: May 2020

Neuropeptides are a structurally diverse class of chemical messengers that play important roles in the coordination of many physiological and behavioural events. Neuropeptides are derived from the cleavage of larger precursor proteins at the dibasic amino acid sites by prohormone convertases. They are synthesised in the cell body, packaged in the large dense core vesicles and released in a neuronal activity‐dependent manner. The neuropeptides may function as blood‐borne hormones or as mediators/transmitters affecting neuronal activity in the nervous system. In the target cells, neuropeptides activate the complementary G protein‐coupled receptors and elicit responses that are specific to these cells. The released peptide is subsequently inactivated by the actions of several nonspecific extracellular peptidases.

Key Concepts

Neuropeptides are a structurally diverse class of chemical messengers produced by nerve cells to coordinate many physiological and behavioural processes.

The major neuroendocrine centre in the brain is the pituitary gland.

Neuropeptides are derived from the cleavage of the larger precursor proteins by specific endoproteases that are copackaged in the dense core secretory granules.

Receptors for neuropeptides belong mainly to the family of G protein‐coupled receptor.

G protein‐coupled receptor may be activated in complex modes beyond their interaction with G proteins.
Microorganisms in High‐Temperature Sulfur Environments
Authors: Bonch‐Osmolovskaya Elizaveta
Published: May 2020

Sulfur‐rich high‐temperature environments such as solfataric fields, hot springs and ‘black smokers’ provide habitats for microbial life at the upper temperature border. Such regions have yielded extremely and hyperthermophilic bacteria and archaea that grow optimally at temperatures above 70 °C, some even above 100 °C.

Key Concepts

Hyperthermophilic and extremely thermophilic bacteria and archaea thrive at high temperature, up to boiling point of water.

They are phylogenetically and metabolically diverse.

They represent deepest phylogenetic linages in prokaryotes.

They perform closed sulfur cycle in thermal environments.

The highest growth temperature is the capacity of microorganisms inhabiting deep‐sea hot vents.
Glioblastoma Models in
Drosophila melanogaster
Authors: Losada‐Pérez María , Jarabo Patricia , Martín‐Castro Francisco A , Casas‐Tintó Sergio
Published: May 2020

Glioblastoma (GB) is the most common and malignant brain tumour with a median survival of 15 months. The genetic basis of GB is heterogeneous, but mutations in EGFR and PI3K pathways are the most frequent. The need of novel models to decipher molecular mechanisms underlying GB progression has brought
Drosophila melanogaster
as an optimal candidate. The power of fly genetics, the development of novel gene expression and visualisation techniques and genetic and drug screenings put
Drosophila
in an advantageous position. Moreover, the evolutionary conserved function of glial cells allows an extrapolation of the results towards a clinical view.

Key Concepts

Glial functions are evolutionary conserved along animal kingdom.

Drosophila
is a suitable model to study gene networks in GB.

The wide collection of experimental tools in
Drosophila
facilitates the modulation and detection of signalling pathways.

Drosophila
is a valid model to validate therapeutical platforms.

Glioblastoma to neuron communication plays a central role in tumor progression and neurodegeneration.
ROS
Crosstalk in Signalling Pathways
Authors: Heap Brittany , Holden Claire , Taylor Jane , McAinsh Martin
Published: May 2020

Plants have evolved complex signalling networks in order to respond to the plethora of environmental and developmental stimuli to which they are exposed. Within these networks, a diverse range of signals are integrated, allowing the plant to formulate an appropriate response to the prevailing conditions. An important feature of signalling pathways into networks is the potential for pathways to interact with each other, thereby influencing the responses observed. This is known as crosstalk. Signalling networks act through a hub and spoke model where the hub is a key determinant of the pathways that will crosstalk with one another. Reactive oxygen species (ROS) are an example of such a signalling hub that play an intrinsic role in crosstalk within plant stress signalling networks. ROS are of particular interest due to their ability to have positive or negative effects, depending on their abundance within the cell.

Key Concepts

Plants employ complex signalling networks in their responses to environmental and developmental stimuli, transducing a wide range of signals from the point of perception, typically via a receptor, to a diverse array of effectors.

Signalling can occur via a range of intermediates (chemical, electrical or hydraulic) including well‐characterised secondary messenger compounds.

Crosstalk can occur between signalling pathways when one or more of these components interact with each other.

ROS are important signalling molecules, essential for plant cell homeostasis and the regulation of vital plant responses, such as reaction to abiotic and biotic stress, hormone signalling and the regulation of growth.

ROS can have a positive or negative effect within a cell, acting as either a toxic by‐product of aerobic respiration within cells or essential signalling molecules through their role as an indispensable hub in plant signalling networks.
Immunoproteasome
Authors: Kimura Hiroaki
Published: May 2020

The immunoproteasome is a proteolytic complex whose five subunits, β1i, β2i, β5i, PA28α and PA28β, are replaced with subunits in the constitutive proteasome. It plays an important role in the immune system and the pathogenesis of inflammatory diseases. In addition, the immunoproteasome regulates the polarisation of immune cells such as M2 macrophages and Th1 and Th17 lymphocytes. While expression of the immunoproteasome is dominant in haematopoietic cells, nonhaematopoietic cells in various peripheral tissues also express the immunoproteasome, and its expression is enhanced by inflammatory cytokines and stress signals. Recent studies indicate that each subunit of the immunoproteasome plays a unique role in nonhaematopoietic cells. For instance, β5i plays a critical role in adipogenesis and metabolic disorders. Furthermore, genetical mutation of the immunoproteasome subunits causes autoinflammatory diseases and lipodystrophy.

Key Concepts

The immunoproteasome plays an important role in the immune system.

The immunoproteasome is involved in the pathogenesis of inflammatory diseases.

Inhibition of the immunoproteasome is useful as a treatment for inflammatory diseases and tumours.

The immunoproteasome plays a unique role in nonhaematopoietic cells.

Deficiency of the immunoproteasome influences endocrine metabolic functions.

Mutation of the immunoproteasome subunit is associated with autoinflammatory diseases and lipodystrophy.
Introduction to the Plant Plasma Membrane
Authors: Miller Anthony J
Published: May 2020

The plasma membrane (PM) surrounds all living cells and is the border checkpoint regulating transport and maintaining cytoplasmic homeostasis. The PM is composed of a phospholipid bilayer containing proteins that are important for transport across this barrier. These transport proteins operate with three different mechanisms, as channels, carriers or pumps. From their amino acid sequences, transporter families of proteins have been identified, and these are often shared across all types of organisms, including bacteria, fungi and animals. Using sequence information, the function of an uncharacterised membrane protein can be defined, identifying the likely substrates carried by the transporter. The PM makes direct contact with the external environment through the cell wall, and some membrane proteins are receptors that sense the changing conditions outside the cell. Receptors help the cell to maintain cytoplasmic homeostasis and detect and fight pathogens.

Key Concepts

Phospholipid bilayers and proteins provide the fundamental architecture of the plasma membrane.

The phospholipid bilayer is not permeable to most ions and molecules, and selective transport is provided by proteins embedded in the membrane.

Three types of transporter mechanisms mediate transport across the plasma membrane, channels, carriers and pumps.

Families of PM transporters have been identified, and it is possible to predict their cargo ions and molecules based on gene sequence similarities.

The PM is a major sensing site containing many different types of receptors perceiving the external environment.

The PM of adjacent plant cells can be connected through plasmodesmatal pores in the cell wall.
Terminal Deoxynucleotidyl Transferase(TdT)
Authors: van Zelm Menno C
Published: May 2020

Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase with the unique capacity to add nucleotides to a DNA strand in an untemplated fashion. This capacity is specifically utilised in developing B‐cells and T‐cells in vertebrates to generate extra diversity in the antigen receptor repertoire. During the process of V(D)J recombination developing B‐ and T‐cell rearrange the DNA encoding the immunoglobulin (Ig) and T‐cell receptor (TCR) genes, respectively. Following the introduction of double‐strand DNA breaks and prior to the ligation by members of the nonhomologous end joining (NHEJ) pathway, TdT can add nontemplated (N‐)nucleotides to the open DNA ends. Through the capacity to generate longer junctions with new nucleotide compositions, TdT is critical in driving the generation of the enormous antigen receptor repertoire with a potential 1015unique sequences that facilitate recognition of the diverse range of pathogens vertebrates are exposed to.

Key Concepts

TdT is a DNA polymerase with nontemplated activity.

TdT adds random nucleotides in the junctional region during V(D)J recombination.

TdT expression is tightly regulated in early B‐ and T‐cell progenitors.

Detection of nuclear TdT expression using recombinant antibodies is an important biomarker for diagnostics and minimal residual disease monitoring of acute leukaemias.

TdT expression is regulated by IL‐7 receptor signalling.

Foetal B‐ and T‐cell progenitors have reduced TdT expression and function.
Membrane Nanodomains
Authors: Goñi Félix M , Alonso Alicia , Contreras F Xabier
Published: May 2020

Biomembranes are assumed to contain lateral heterogeneities, usually called domains. When they are less than ∼100 nm in diameter, they are referred to as nanodomains. Biological nanodomains have been properly identified only in the twenty first century, largely through the advent of super‐resolution microscopy techniques. Size, irrespective of lifetime, is used as a defining parameter for nanodomains. The main methods used in these studies span from the arguably earliest atomic force microscopy detection of nanodomains in a lipid bilayer, in year 2000, to the most recent observations in living cells of synapsis, receptors, exocytosis or plant membranes, based on advanced fluorescence microscopy techniques.

Key Concepts

Nanodomains are lateral inhomogeneities in lipid bilayers or in cell membranes, of varying lifetimes, and diameters usually below ≈200 nm.

Nanodomains are stabilised by low line tensions and high dipole–dipole interactions and crowding pressures.

Observation of nanodomains requires the use of atomic force microscopy and super‐resolution fluorescence microscopy as the main tools.
GABA
A
Receptor Modulators
Authors: Ernst Margot , Silva Luca L , Vogel Florian D
Published: May 2020

Allosteric modulators are molecules that act at sites different from orthosteric sites and influence the effects of orthosteric ligands on the target protein. For the family of GABA
A
receptors, allosteric modulation is a key concept exploited by widely used pharmaceuticals, for example tranquilisers of the benzodiazepine type or sedative anaesthetics such as etomidate. Recent developments reflect efforts to identify the binding sites involved in such allosteric modulation and the selective targeting of individual receptor subtypes. The precise number and structures of native GABA
A
receptor subtypes are still not known. A widely used useful distinction refers to synaptic and extrasynaptic pools of receptors, and some progress has been made in targeting these pools separately. A recent surge identified endogenous modulators, among them endocannabinoids and dopamine. As knowledge about modulators as well as their binding sites increases, development of more selective agents will be facilitated.

Key Concepts

Clinically used drugs targeting GABA
A
receptors are mostly allosteric modulators – benzodiazepines and sedative narcotics are prominent examples.

Allosteric modulators change agonist function in various ways by interactions with allosteric modulatory sites.

Diverse effects have been categorised; acronyms such as PAM type I and similar are used – but the terminology is not standardised.

Functional selectivity has been introduced as a term to differentiate selective action from selective binding.

For many chemotypes the exact binding sites on GABA
A
receptors are not yet known; structural knowledge is still needed.

While receptors consisting of alpha, beta and gamma subunits are very well characterised, much less is known about receptors that contain only alpha and beta subunits and receptors that contain delta, pi, theta, epsilon or rho subunits.
Polyandry and Mating System Evolution
Authors: Boulton Rebecca A
Published: May 2020

Our understanding of animal mating systems has been considerably enhanced in recent years by the development of molecular methods to reliably assay female multiple mating (polyandry). These techniques have demonstrated that polyandry is widespread across animal groups, even in species thought to be strictly monogamous and pair‐bonded. The research that has arisen from this paradigm shift has shown that females can gain substantial material benefits from mating with multiple males, in terms of increased fecundity, infanticide avoidance and sperm replenishment. Polyandry can also provide indirect or genetic benefits to females, increasing the likelihood that they will mate with at least one compatible or high‐quality male. By mating multiply females can also increase the genetic diversity of their offspring, which may be advantageous in changeable environments. Importantly polyandry has demonstrated that mating systems extend beyond copulation and sexual selection occurs not just over mates but also over their gametes.

Key Concepts

Recent developments in molecular ecology have allowed researchers to rapidly and easily test whether multiple fathers sire female offspring.

Multiple mating by females (polyandry) is now known to be widespread across taxa.

While mating can be costly, polyandry has been shown to provide substantial benefits to females.

Direct, or material benefits of polyandry increase female offspring production, for instance by providing females with additional resources in nuptial gifts or seminal fluids.

Indirect, or genetic benefits of polyandry arise when multiple mating increases the chances that a female mates with at least one compatible or high‐quality male.

Polyandry can also increase offspring genetic diversity, and this can be beneficial in unstable or harsh environments, increasing the chances that at least some offspring will survive.

Polyandry means that sexual selection continues after mating, males compete not only for mates but also their gametes (post‐copulatory sexual selection).

Post‐copulatory sexual selection can render certain male traits beneficial, which can alter the costs and benefits of polyandry for females and change the optimal female mating rate.

As a result of the realisation that polyandry is widespread, mating systems research now integrates formerly unappreciated concepts such as sperm competition, cryptic female choice and co‐evolutionary feedbacks between male and female mating strategies.
Inversions and Evolution
Authors: Westram Anja M , Faria Rui , Butlin Roger , Johannesson Kerstin
Published: May 2020

Inversions are chromosomal rearrangements where the order of genes is reversed. Inversions originate by mutation and can be under positive, negative or balancing selection. Selective effects result from potential disruptive effects on meiosis, gene disruption at inversion breakpoints and, importantly, the effects of inversions as modifiers of recombination rate: Recombination is strongly reduced in individuals heterozygous for an inversion, allowing for alleles at different loci to be inherited as a ‘block’. This may lead to a selective advantage whenever it is favourable to keep certain combinations of alleles associated, for example under local adaptation with gene flow. Inversions can cover a considerable part of a chromosome and contain numerous loci under different selection pressures, so that the resulting overall effects may be complex. Empirical data from various systems show that inversions may have a prominent role in local adaptation, speciation, parallel evolution, the maintenance of polymorphism and sex chromosome evolution.

Key Concepts

Inversions are chromosomal rearrangements where the order of loci is reversed.

Inversions can be under negative, positive or balancing selection.

A key effect is that they reduce recombination in individuals heterozygous for the arrangement.

They therefore facilitate the maintenance of ‘blocks’ of associated alleles.

This is favourable under local adaptation, positive epistasis and frequency‐dependent selection favouring multiple different morphs in a population.

Accordingly, inversions have been shown to contribute to the maintenance of within‐species polymorphism and between‐species divergence in various empirical studies.

Inversions also contribute to speciation by coupling different barriers to gene flow.

Finally, they also contribute to sex‐chromosome differentiation and degeneration.

Identifying the targets of selection within inversion is challenging but possible, at least for old inversions.

Knowing the evolutionary history of inversions is fundamental to understanding their influence in adaptation and speciation.
Accelerated Life Tests: Classical Methods for Design and Analysis
Authors: Giorgio Massimiliano
Published: May 2020

Accelerated life tests are used to obtain quickly information about the failure time distribution of very reliable technological products. Tests are conducted in conditions more severe than the normal operating ones with the aim of accelerating the mechanism of failure and thus shortening the life of components and materials of interest.

An estimate of lifetime distribution at normal use conditions is extrapolated from data obtained at higher stresses by using appropriate statistical models, which incorporate special relationships accounting for the effect of stress on lifetime of products under study.

After a brief introduction that describes motivations and objectives of accelerated testing, the following topics are addressed:

Methods for accelerating reliability tests.

Models for classical accelerated tests.

Procedures for point estimation, interval estimation, and model checking.

Basic criteria for planning accelerate life tests.

In this article, only classical fully parametricestimationprocedures are discussed. Moreover, only models for constant stress ALT data are considered, that is, data obtained by running tests at constant stress with a single accelerating variable. All the models presented in this paper are for single failure mode: they cannot be used for products that may fail in more than one mode.
Integrated Nested Laplace Approximations
(INLA)
Authors: Martino Sara , Riebler Andrea
Published: May 2020

The integrated nested Laplace approximation (INLA) approach provides approximate Bayesian inference in latent Gaussian models (LGMs). INLA relies on a combination of analytical approximations and efficient numerical integration schemes to achieve highly accurate deterministic approximations to posterior quantities of interest. The main benefit of using INLA instead of Markov chain Monte Carlo (MCMC) techniques for LGMs is computational; INLA is fast even for large, complex models. Moreover, being a deterministic algorithm, INLA does not suffer from slow convergence and poor mixing. INLA is implemented in the R package
R‐INLA
, which represents a user‐friendly and versatile tool for doing Bayesian inference.
R‐INLA
returns posterior marginals for all model parameters and the corresponding posterior summary information. Model choice criteria as well as predictive diagnostics are directly available. Here, we outline the theory behind INLA, present the
R‐INLA
package, and describe new developments of combining INLA with MCMC for models that are not possible to fit with
R‐INLA
.
Model Selection in Regression: Statistical and Scientific Perspectives
Authors: Denis Daniel J.
Published: May 2020

Model selection in regression and the choice of what might be considered a
best
model is often fraught with difficulty. This article briefly reviews select topics in model and variable selection, both from a statistical and scientific point of view. Topics discussed include the importance of selecting good candidate predictors; simultaneous inference in regression; best subsets selection; penalized fit statistics and ridge regression; lasso; backward, forward, and stepwise algorithms; and statistical versus pragmatic model selection. It is concluded that in addition to statistical criteria, substantive utility and usability of a model should also be incorporated into the final model selection.