bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

AbstractTerminal 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 ConceptsTdT 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

Abstract

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

Abstract

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

AbstractOur 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 ConceptsRecent 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

Abstract

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

AbstractAccelerated 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

Abstract

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

Abstract

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.