Publications
Now showing items 901-1000 of 1372
The Physiological Functions of the Amyloid Precursor Protein Gene Family
(2017)
The amyloid precursor protein APP plays a key role in the pathogenesis of Alzheimer’s disease (AD), as proteolytical cleavage of APP gives rise to the Aß peptide which is deposited in the brains of Alzheimer patients. ...
Physiological and molecular ecology of aquatic cyanobacteria
(2015)
The cyanobacteria inhabit every illuminated environment on Earth, from polar lakes to desert crusts and through their phototrophic metabolism play essential roles in global geochemical cycles. With the discovery of marine ...
Physiological Adaptations to Swimming in Fish
(2017)
Swimming is an integral part of the life history of many fish species as is intimately linked with their ability to express feeding and predator avoidance behaviors, habitat selection and environmental preferences, social ...
Planctomycetes-Verrucomicrobia-Chlamydiae Bacterial Superphylum: New Model Organisms for Evolutionary Cell Biology
(2017)
The Planctomycetes, Verrucomicrobia, Chlamydiae (PVC) and related phyla have recently emerged as fascinating subjects for research in evolutionary cell biology, ecology, biotechnology, evolution and human health. This ...
New edge of antibiotic development: antimicrobial peptides and corresponding resistance
(2014)
Antimicrobial peptides, commonly isolated from several organisms, have been considered part of innate immune system and also as potential antimicrobial drugs. Besides its antimicrobial activity, some AMPs also have antifungal ...
New Trends on Genome and Transcriptome Characterizations
(2018)
This Research Topic is devoted to bioinformaticians, geneticists and researchers who study or apply methods and algorithms for genomes and transcriptome analyses, aimed at understanding pathology discriminations and ...
Mathematical and Statistics Anxiety: Educational, Social, Developmental and Cognitive Perspectives
(2017)
Mathematical anxiety is a feeling of tension, apprehension or fear which arises when a person is faced with mathematical content. The negative consequences of mathematical anxiety are well-documented. Students with high ...
Platelets as immune cells in physiology and immunopathology
(2015)
Are platelets cells? (Not everyone agrees, since they are non-nucleate). And if platelets are cells - which all specialists consider at the time being - are they immune cells? The issue that platelets participate in immunity ...
Plastid Proteostasis: Relevance of Transcription; Translation and Post-Translational Modifications
(2017)
Due to their bacterial endosymbiotic origin plastids are organelles with both nuclear-encoded and plastid-encoded proteins. Therefore, a highly integrated modulation of gene expression between the nucleus and the plastome ...
Plasticity of primary afferent neurons and sensory processing after spinal cord injury
(2015)
Traumatic injury of the spinal cord affects the entire organism directly and indirectly. Primary injury destroys neurons and severs axons which participate in neural circuits. Secondary injuries and pathologies arise from ...
Plasticity of GABAergic synapses
(2016)
Learning and memory are believed to depend on plastic changes of neuronal circuits due to activity-dependent potentiation or depression of specific synapses. During the last two decades, plasticity of brain circuits was ...
Optical Approaches to Capture Plant Dynamics in Time, Space, and Across Scales
(2018)
Quantifying temporal changes in plant geometry as a result of genetic, developmental, or environmental causes is essential to improve our understanding of the structure and function relationships in plants. Over the last ...
The oral microbiome in an ecological perspective
(2015)
The oral cavity harbors an immense diversity of microorganisms, including bacteria, fungi, archaea, protozoa and viruses. At health, oral microbial community is thought to be in a state of homeostasis, even after numerous ...
Perceiving and Acting in the Real World: From Neural Activity to Behavior
(2016)
One remarkable ability of the human brain is to process large amounts of information about our surroundings to allow us to interact effectively with them. In everyday life, the most common way to interact with objects is ...
Perception of visual advertising in different media: from attention to distraction, persuasion, preference and memory
(2015)
This Research Topic aims to showcase the state of the art in visual advertising research. Although visual processes are a central component of consumer behavior, they have been largely neglected in models explaining consumer ...
Perception and Cognition: Interactions in the Ageing Brain
(2016)
Healthy ageing can lead to declines in both perceptual and cognitive functions. Impaired perception, such as that resulting from hearing loss or reduced visual or tactile resolution, increases demands on ‘higher-level’ ...
Personalized Medicine and Neurosurgery
(2017)
The Precision Medicine Initiative, which was instituted by President Barack Obama on January 20, 2015, highlighted the importance that advances in genomics and related “-omic” approaches have made to science and medicine, ...
Origin and spatiotemporal dynamics of the peroxisomal endomembrane system
(2015)
The peroxisome is an organelle with essential roles in lipid metabolism, maintenance of reactive oxygen species homeostasis, and anaplerotic replenishment of tricarboxylic acid cycle intermediates destined for mitochondria. ...
The Origin of the Plasma Cell Heterogeneity
(2015)
Plasma cells (PCs) are terminally differentiated B-cells producing large amounts of immunoglobulins (Ig). In humans, most of circulating Ig are produced by bone marrow plasma cells. PCs differentiate from activated naïve ...
Paradigm changes are required in HIV vaccine research
(2015)
In his 1962 book "The Structure of Scientific Revolutions", Thomas Kuhn famously argued that researchers in every field of scientific enquiry always operate under a set of presuppositions known as paradigms that are rarely ...
Podocyte Pathology and Nephropathy
(2015)
The understanding of the pathogenesis of diabetic nephropathy (DN) has advanced considerably in the last few years. Much has been learned about the natural history, the relative lack of significance of microalbuminuria in ...
Phonology in the Bilingual and Bidialectal Lexicon
(2017)
A conversation between two people can only take place if the words intended by each speaker are successfully recognized. Spoken word recognition is at the heart of language comprehension. This automatic and smooth process ...
Phonological and phonetic competence: between grammar, signal processing, and neural activity
(2016)
The present collection of articles brings together experimental work in the field of segmental and prosodic processing and representation in phonology and phonetics. Contributions focus on the exploration of human cognitive, ...
PI3K signalling
(2015)
The PI3Ks control many key functions in immune cells. PI3Ks phosphorylate PtdIns(4,5)P2 to yield PtdIns(3,4,5)P3. Initially, PI3K inhibitors such as Wortmannin, LY294002 and Rapamycin were used to establish a central role ...
New Frontiers in Multiscale Modelling of Advanced Materials
(2016)
Atomistic simulations, based on ab-initio and semi-empirical approaches, are nowadays widespread in many areas of physics, chemistry and, more recently, biology. Improved algorithms and increased computational power widened ...
New frontiers in the neuropsychopharmacology of mental illness
(2015)
In recent years, mental illnesses have become recognized as a huge emotional and financial burden to the individual, their relatives and society at large. Stress-related and mood disorders as well as psychoactive substance ...
Novel Therapeutic Targets and Emerging Treatments for Fibrosis
(2018)
For decades we have known that the overgrowth, hardening and scarring of tissues (so-called fibrosis) represents the final common pathway and best histological predictor of disease progression in most organs. Fibrosis is ...
Novel roles of non-coding brain RNAs in health and disease
(2014)
Non-coding RNAs (ncRNAs), and in particular microRNAs are rapidly becoming the focus of research interest in numerous basic and translational fields, including brain research; and their importance for many aspects in brain ...
Measurement Invariance
(2015)
Multi-item surveys are frequently used to study scores on latent factors, like human values, attitudes and behavior. Such studies often include a comparison, between specific groups of individuals, either at one or multiple ...
Open questions on the mechanisms of neuromodulation with applied and endogenous electric fields
(2015)
Despite increased knowledge, and more sophisticated experimental and modeling approaches, fundamental questions remain about how electricity can interact with ongoing brain function in information processing or as a medical ...
Organic Ligands in Marine Trace Metal Biogeochemistry
(2018)
This research topic highlights the most recent accomplishments of a Scientific Committee on Oceanic Research (SCOR) Working Group, SCOR WG 139: Organic Ligands - A Key Control on Trace Metal Biogeochemistry in the Ocean.
Nucleation and Crystallization of Glasses and Glass-Ceramics
(2017)
The E-book "Nucleation and Crystallization of Glasses and Glass-Ceramics" highlights historic perspectives and current research in the field of glass-ceramic technology. Glass-ceramic technology is promising to provide us ...
The origin, function and diagnostic potential of extracellular microRNA in human body fluids
(2014)
Short non-coding RNA molecules, microRNAs (miRNAs), post-transcriptionally regulate gene expression in living cells. In recent years, miRNAs have been found in a wide spectrum of mammalian body fluids including blood plasma, ...
Origin of Tropical Diversity: From Clades to Communities
(2017)
In this volume we aimed to assess progress in determining the processes by which current patterns of tropical biodiversity were established and are maintained. Tropical regions are highly species-rich and we present studies ...
The Parallel March of Asthma and Allergy in Childhood: A Multi-Perspective Approach
(2018)
It has not been yet clarified whether allergy and asthma are part of the same condition or they follow a parallel path. This Research Topic aims to try and put some light in this parallel march going through crucial topics: ...
Pathogenic Advances and Therapeutic Perspectives for Eosinophilic Inflammation
(2018)
With the recent approval of the first eosinophil-depleting therapeutic agents targeting the IL-5 pathway for treatment of severe eosinophilic asthma, eosinophils and eosinophilic disorders are in the limelight. Indeed, ...
The pathogenic Yersiniae - advances in the understanding of physiology and virulence
(2014)
For decades, pathogenic Yersinia have served as an inventive model organism for researchers seeking to understand the complexities of bacteria-host cell interactions. In fact, seminal studies on Yersinia virulence mechanisms ...
The Pathogenetic Mechanisms at the Basis of Aortopathy Associated with Bicuspid Aortic Valve: Insights from "Omics", Models of Disease and Emergent Technologies
(2018)
This forum of comprehensive reviews and research studies on distinct aspects of the pathophysiology of BAV aortopathy provides both the state of the art in the knowledge on this complex disease and novel insights into its ...
Pathologic Conditions of the Human Nervous and Muscular Systems Associated with Mutant Chaperones: Molecular and Mechanistic Aspects
(2018)
This eBook presents illustrative examples of genetic chaperonopathies affecting primarily nerves and muscles and discusses molecular mechanisms and treatment targeting chaperones, i.e., chaperonotherapy.
Pathogenesis of Leptospira
(2018)
The present eBook, consisting of a compilation of research and review articles, focuses on the features and mechanisms adopted and explored by pathogenic leptospires to successfully establish infection in the host. ...
The Physiology and Pharmacology of Leucine-rich Repeat GPCRs
(2016)
G protein-coupled receptors (GPCRs) represent a large and physiologically important class of cell surface receptors. There are approximately 750 known GPCRs present in the human genome that can be subdivided into general ...
Physiology and Pathophysiology of the Extracellular Calcium-Sensing Receptor
(2018)
Calcium is vital for human physiology; it mediates multiple signaling cascades, critical for cell survival, differentiation, or death both as first and as second messenger. The role of calcium as first messenger is mediated ...
Physiology and Pathophysiology of Musculoskeletal Aging
(2015)
We live in a world with an ever-increasing aging population. This aging population is predicted to place a huge financial burden on healthcare systems around the world. Understanding healthy ageing is a key research priority, ...
Physiology in Extreme Conditions: Adaptations and Unexpected Reactions
(2017)
Physiology in extreme conditions can reveal important reactions of the human body, which help our assessment of limits emerging under healthy conditions and critical signals of transition toward disease. While many mechanisms ...
Never-resting microglia: physiological roles in the healthy brain and pathological implications
(2015)
Microglia are largely known as the major orchestrators of the brain inflammatory response. As such, they have been traditionally studied in various contexts of disease, where their activation has been assumed to induce a ...
New Advances in Electrocochleography for Clinical and Basic Investigation
(2018)
Electrocochleography (ECochG) is an approach for objective measurements of physiologic responses from the inner ear. Measurements have classically been made from electrodes placed in the outer ear canal, on the tympanic ...
Plasticity in the sensory systems of invertebrates
(2014)
The visual, olfactory, auditory and gustatory systems of invertebrates are often used as models to study the transduction, transmission and processing of information in nervous systems, and in recent years have also provided ...
Plastic Surgery for the Oncological Patient
(2016)
The develoment of plastic surgery techniques allows for preserving and reconstruction of function after resection of malignant tumors. From split thickness skin grafts to pedicled and free tissue transfer multiple techniques ...
Plasticity in Multiple Sclerosis: From Molecular to System Level, from Adaptation to Maladaptation
(2016)
This research topic aims at providing a state of the art update on neuroplasticity in humans with multiple sclerosis. It summarizes advances in plasticity research as achieved by a variety of techniques, in the motor as ...
Plastic Pollution
(2017)
The presence, at sea, of large amounts of plastic and microplastics, which are sometimes invisible and results from the fragmentation of larger debris, requires an in-depth knowledge of the nature of ocean debris, its ...
Optimizing the Delivery of Multiple Ecosystem Goods and Services in Agricultural Systems
(2017)
Agricultural land is subjected to a variety of societal pressures, as demands for food, animal feed, and biomass production increase, with an added requirement to simultaneously maintain natural areas and mitigate climatic ...
Optimizing Miscanthus for the Sustainable Bioeconomy: From Genes to Products
(2018)
In this Research Topic we report advances in fundamental and applied aspects of the perennial C4 bioenergy crop Miscanthus (Miscanthus spp.) and its role in mitigating climate change as part of the bioeconomy. Miscanthus ...
Pedagogical Psychology: Beyond the 21st Century
(2015)
Frontiers in Psychology is introducing a new research topic, Pedagogical Psychology: Beyond the 21st Century, which will be released as an online journal issue in summer 2014. The purpose of Beyond the 21st Century will ...
Peripheral Nervous System-Machine Interfaces, 2nd Edition
(2018)
For 5 years, the Peripheral Nervous System-Machine Interfaces workgroup has dedicated itself to the recruitment of researchers, clinicians, and general public in a unified effort to advance the frontier of restoration of ...
Peripheral Nervous System-Machine Interfaces
(2018)
For 5 years, the Peripheral Nervous System-Machine Interfaces workgroup has dedicated itself to the recruitment of researchers, clinicians, and general public in a unified effort to advance the frontier of restoration of ...
Pain Management in Clinical and Health Psychology
(2018)
Chronic pain is a relevant health problem frequently associated with psychological distress, dysfunctions in physical and social functioning, reductions in quality of life and elevated direct and indirect costs. Medical ...
PAIN - Novel targets and new technologies
(2015)
The problem of clinical pain management is complex and far-reaching, as it encompasses many different types of pain, such as arthritis, musculoskeletal conditions, neuropathic pain, and visceral pain. It is widely known ...
Photonic Integration and Photonics-Electronics Convergence on Silicon Platform
(2015)
Silicon photonics technology, which has the DNA of silicon electronics technology, promises to provide a compact photonic integration platform with high integration density, mass-producibility, and excellent cost performance. ...
New Boundaries Between Aging, Cognition, and Emotions
(2018)
Numerous studies have reported age-related differences for emotional information. For example, when, compared to younger adults, older adults reveal a relative preference in attention and memory for positive over negative ...
New Advanced Wireless Technologies for Objective Monitoring of Motor Symptoms in Parkinson's Disease
(2018)
Over the last decade, a growing number of researchers have used advanced wireless technologies including wearable sensors for objective evaluation of specific motor symptoms in patients with Parkinson's disease (PD). In ...
New treatment perspectives in autism spectrum disorders
(2015)
Developing novel and more effective treatments that improve quality of life for individuals with autism spectrum disorders is urgently needed. To date a wide range of behavioral interventions have been shown to be safe and ...
New therapeutic targets for human placental angiogenesis diseases
(2015)
A large number of publications have described impaired angiogenesis and vasculogenesis present in the feto-placental circulation after pregnancy diseases such as pre-eclamptic pregnancies, gestational diabetes, and ...
New Translational Insights on Metabolic Syndrome: Obesity, Hypertension, Diabetes and Beyond
(2016)
Metabolic syndrome (MetS) can be considered as a clustering of several risk factors such as obesity, hypertension, insulin resistance and dyslipidemia, which could lead to the development of diabetes and cardiovascular ...
New Therapies and Immunological Findings in Melanoma and Other Skin Cancers
(2019)
New therapies are currently being developed in the field of skin cancer. In particular, advances in melanoma now represent the frontline of cancer immunotherapy, as immunological findings in the disease have led to the ...
Non-Ordinary Mental Expressions
(2015)
So-called altered states of consciousness (ASC) are an intriguing, still under-researched topic, with profound neuropsychological and epistemological implications. In the last few decades there has been increasing ...
Non-Polysaccharide Plant Polymeric Materials
(2016)
Plants are the most important renewable source of feedstock for polymeric materials. They are a resource of monomers and macromolecules after the appropriate chemical treatment. By analogy with the petrochemistry industry, ...
Non-Pharmacological Interventions for Schizophrenia: How Much Can Be Achieved and How?
(2017)
The introduction of antipsychotic agents in the 1950’s substantially improved the treatment of schizophrenia and other psychotic disorders. However, clinical and functional outcomes are still far less than optimal for ...
Optogenetic Tools in the Molecular Spotlight
(2016)
The rise of optogenetics as a standard technique to non-invasively probe and monitor biological function created an immense interest in the molecular function of photosensory proteins. These photoreceptors are usually ...
Personality and Cognition in Economic Decision Making
(2017)
Psychologists studying cognitive processes and personality have increasingly benefited from the wealth of theory, methodology, and decision making paradigms used in economics and game theory. Similarly, for the economists, ...
Paleoecology of Easter Island: Natural and Anthropogenic Drivers of Ecological Change
(2018)
After more than three decades of paleoecological research, the potential role of climatic and anthropogenic drivers on Easter Island's ecological and cultural change is still under discussion. This eBook aims to provide ...
Parasites in the Tropic - A New Paradigm Shift
(2017)
The highlight of this eBook is to bring new insights into parasites in the tropic. To achieve that, much has been discussed about risk assessment, infection rates, disease burden, hormones and mechanism of immune response, ...
Parasite Infections: From Experimental Models to Natural Systems
(2018)
Eukaryotic parasites (including parasitic protozoans, worms and arthropods) are more complex and heterogeneous organisms than pathogenic bacteria and viruses. This notion implies different evolutionary strategies of host ...
Phenotypic screening in the 21st century
(2015)
In the genomic era of 1990s-2000s, pharmaceutical research moved to target-based drug discovery which enabled development of a number of small molecule drugs against a wide range of diseases. In many cases however, drugs ...
Phenomics
(2018)
"Phenomics" is an emerging area of research whose aspiration is the systematic measurement of the physical, physiological and biochemical traits (the phenome) belonging to a given individual or collection of individuals. ...
New Approaches to the Pathogenesis of Sudden Intrauterine Unexplained Death and Sudden Infant Death Syndrome
(2017)
Sudden Infant Death Syndrome (SIDS) is the leading cause of death among infants in the first year of age. The more known definition of SIDS is the sudden unexpected death of an infant less than 1 year of age, with onset ...
New Insights into Microbial Ecology through Subtle Nucleotide Variation
(2016)
The 16S ribosomal RNA gene commonly serves as a molecular marker for investigating microbial community composition and structure. Vast amounts of 16S rRNA amplicon data generated from environmental samples thanks to the ...
New Insights on Basic and Clinical Aspects of EEG and MEG Connectome
(2018)
Recent advances in the neuroimaging field areas allow us to visualize the aggregate of neural connections at the macroscopic level within the brain, the so-called “connectome”. In order to promote the development of the ...
Non-invasive Brain Stimulation in Neurology and Psychiatry
(2017)
Brain stimulation techniques, transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (TDCS), modify brain function through interaction with multiple neurotransmitters and networks. The ...
Non-conventional Yeast in the Wine Industry
(2017)
Saccharomyces cerevisiae strains that exhibit high ethanol tolerance and excellent fermentative ability are extensively used in winemaking as selected starters. However, a side-effect of the widespread use of these commercial ...
Novel Approaches to the Analysis of Family Data in Genetic Epidemiology
(2016)
Genome-wide association studies (GWAS) for complex disorders with large case-control populations have been performed on hundreds of traits in more than 1200 published studies (http://www.genome.gov/gwastudies/) but the ...
Novel Aspects of Nucleolar Functions in Plant Growth and Development
(2018)
The nucleolus is a prominent nuclear domain that is common to eukaryotes. Since the nucleolus was first described in the 1830s, its identity had remained a mystery for longer than 100 years. Major advances in understanding ...
Matricellular Receptors as Potential Targets in Anti-Cancer Therapeutic Strategies
(2016)
The invasive character of a primary cancer is greatly dependent on numerous interactions between tumor cells and their extracellular surroundings. Matricellular receptors are defined as (cell-surface) receptors that bind ...
Ontogeny and Phylogeny of Brain Barrier Mechanisms
(2016)
The brain functions within an internal environment that is determined and controlled by morphological structures and cellular mechanisms present at interfaces between the brain and the rest of the body. In vertebrates these ...
Online and Offline Modulators of Motor Learning
(2017)
Both the acquisition of new and the modification of previously acquired motor skills are necessary to achieve optimal levels of motor performance in everyday functioning as well as to attain expert performance levels that ...
Perception-Cognition Interface and Cross-Modal Experiences: Insights into Unified Consciousness
(2017)
The present Research Topic explores closely related aspects of mental functioning, namely an interplay between perception and cognition, interactions among various sensory modalities, and finally, more or less unified ...
Perceptual Linguistic Salience: Modeling Causes and Consequences
(2017)
Recent years have seen an upsurge of interest in the notion of salience in linguistics and related disciplines. While in top-down salience, perceivers endogenously direct their attention to a certain stimulus, in the ...
Perception, Action, and Cognition
(2016)
Even as simple a task as quenching thirst with a glass of water involves a sequence of perceptions and actions woven together by expectations and experience. What are the myriad links between perception and action, and ...
Perspective Taking: Building a neurocognitive framework for integrating the "social" and the "spatial"
(2015)
Background: Interacting with other people involves spatial awareness of one’s own body and the other’s body and viewpoint. In the past, social cognition has focused largely on belief reasoning, which is abstracted away ...
Perspectives for the Next Generation of Virus Research: Spearheading the Use of Innovative Technologies and Methodologies
(2017)
Infectious diseases are associated with approximately 20% of global mortality, with viral diseases causing about one third of these deaths. Besides newly emerging and re-emerging viral infections will continue to pose a ...
Parochial Altruism: Pitfalls and Prospects
(2016)
A number of recent influential publications have promoted the idea that the high levels of altruism and violent intergroup conflicts observed in humans might be the result of a joint evolution of behavioral traits causing ...
Plant Competition in a Changing World
(2017)
Competitiveness describes a key ability important for plants to grow and survive abiotic and biotic stresses. Under optimal, but particularly under non-optimal conditions, plants compete for resources including nutrients, ...
Plant Glycobiology - a sweet world of lectins, glycoproteins, glycolipids and glycans
(2014)
Plants synthesize a wide variety of unique glycan structures which play essential roles during the life cycle of the plant. Being omnipresent throughout the plant kingdom, ranging from simple green algae to modern flowering ...
Plant responses to flooding
(2015)
Global warming has dramatically increased the frequency and severity of flooding events worldwide. As a result, many man-made and natural ecosystems have become flood-prone. For plants, the main consequence of flooding is ...
Plant Responses to Biotic and Abiotic Stresses: Lessons from Cell Signaling
(2017)
Facing stressful conditions imposed by their environment and affecting their growth and their development throughout their life cycle, plants must be able to perceive, to process and to translate different stimuli into ...
Plant polyamines in stress and development
(2014)
Polyamines are small aliphatic polycations which have been involved in key stress and developmental processes in plants. In the recent years, compelling genetic and molecular evidences point to polyamines as essential ...
The Proceedings from Halophiles 2013, the International Congress on Halophilic Microorganisms
(2015)
The Halophiles 2013 meeting is a multidisciplinary international congress, with a strong history of regular triennial meetings since 1978. Our mission is to bring researchers from a wide diversity of investigation interests ...
Quantum Structures in Cognitive and Social Science
(2016)
Traditional approaches to cognitive psychology correspond with a classical view of logic and probability theory. More specifically, one typically assumes that cognitive processes of human thought are founded on the Boolean ...
Processing Across Languages
(2018)
The Research Topic aims to highlight research on the processing of words, sentences and discourses across languages. Articles representing processing in a wide variety of human languages will be featured. Efforts will be ...
Promiscuous functions of the prion protein gene family
(2015)
The cellular prion protein PrPC is a ubiquitous GPI-anchored protein. While PrPC has been the focus of intense research for its involvement in a group of neurodegenerative disorders known as transmissible spongiform ...
Psychological perspectives on expertise
(2015)
Experts are persons who are very knowledgeable about or skillful in a particular area. The aim of this Research Topic is to advance knowledge in the understanding of the phenomenon of expertise by putting together different ...