Endogenous Mechanisms Research Articles

Epiphanes brachionus spinosa from a temporary habitat in the Chihuahuan Desert: Morphological response to Asplanchna and control of sexual reproduction

Abstract The rotifer Epiphanes brachionus spinosa occurs in shallow temporary waters with hydroperiods up to several months in the Chihuahuan Desert (U.S.A. and Mexico). Clonal populations from one such habitat were initiated from stem females hatched from fertilised resting eggs in flooded dried sediment, and cultured with the alga Cryptomonas erosa at 19°C in a photoperiod (L:D 16:8). Experiments show that the rotifer has: (1) a morphological response to the predatory rotifer Asplanchna, with which it can co‐occur; and (2) an early and constant propensity for sex and resting‐egg production during population development. Stem females, and females from later generations, have two posterior spines. Measurements of live juveniles and adults indicate that spine length increases isometrically during postnatal growth. Presence of live Asplanchna brightwellii, or its kairomone in Asplanchna‐conditioned medium, significantly increase spine length. In one clone, spine lengths of juvenile Epiphanes from cultures with or without live Asplanchna were, respectively, c. 40 and c. 27 μm. In that clone, spine lengths of adult Epiphanes in cultures with or without Asplanchna kairomone were, respectively, c. 54 and c. 37 μm. In another clone, these spine lengths were, respectively, c. 44 and c. 36 μm. Asplanchna‐induced spine elongation may act as a mechanical defence against capture and ingestion by the predator. Sexual reproduction in E. brachionus spinosa populations is initiated soon after populations develop from stem females and then continues at a rate allowing both population growth by female parthenogenesis and production of resting eggs. Resting eggs hatched after 6–12 days at 19°C. Stem females were amictic (producing daughters parthenogenetically) but produced some daughters that were mictic (producing haploid males parthenogenetically or fertilised resting eggs). In subsequent generations tested 2–7 weeks after hatching of stem females, amictic females from three clonal populations produced similar proportions of mictic daughters (mean c. 0.25) when cultured singly in large volumes (15 and 40 ml) or a small one (1.5 ml). Mictic‐female production is probably automatic and controlled by an endogenous mechanism, rather than specifically induced by crowding or some other environmental factor. Early and continuous sexual reproduction assures production of resting eggs throughout short and unpredictable hydroperiods.

Roles of mitochondrial dynamics and mitophagy in diabetic myocardial microvascular injury.

Myocardial microvessels are composed of a monolayer of endothelial cells, which play a crucial role in maintaining vascular barrier function, luminal latency, vascular tone, and myocardial perfusion. Endothelial dysfunction is a key factor in the development of cardiac microvascular injury and diabetic cardiomyopathy. In addition to their role in glucose oxidation and energy metabolism, mitochondria also participate in non-metabolic processes such as apoptosis, intracellular ion handling, and redox balancing. Mitochondrial dynamics and mitophagy are responsible for regulating the quality and quantity of mitochondria in response to hyperglycemia. However, these endogenous homeostatic mechanisms can both preserve and/or disrupt non-metabolic mitochondrial functions during diabetic endothelial damage and cardiac microvascular injury. This review provides an overview of the molecular features and regulatory mechanisms of mitochondrial dynamics and mitophagy. Furthermore, we summarize findings from various investigations that suggest abnormal mitochondrial dynamics and defective mitophagy contribute to the development of diabetic endothelial dysfunction and myocardial microvascular injury. Finally, we discuss different therapeutic strategies aimed at improving endothelial homeostasis and cardiac microvascular function through the enhancement of mitochondrial dynamics and mitophagy.

Radio Frequency Fingerprinting Identification of Few-Shot Wireless Signals Based on Deep Metric Learning

As a cross-protocol endogenous security mechanism, the physical layer-based radio frequency (RF) fingerprinting can effectively enhance the existing password-based application layer authentication utilizing the hardware differences of wireless devices, which is unique and cannot be counterfeited by a third party. However, the recognition performance of the deep learning physical layer fingerprint recognition algorithm drops sharply in the case of a small number of signal samples. This paper analyzes the feasibility and proposes the few-shot wireless signal classification network based on deep metric learning (FSig-Net). FSig-Net reduces the model’s dependence on big data by adaptively learning the feature distance metric. We use 8 mobile phones and 18 Internet of Things (IoT) modules as targets for identification. When the number of single-type samples is only 10, the recognition accuracy of mobile phones can reach 98.28%, and the recognition accuracy of IoT devices can reach 98.20%.

“Realization–Feedback” Path of Ecological Product Value in Rural Areas from the Perspective of Capital Recycling Theory: A Case Study of Zhengjiabang Village in Changyang County, China

Transforming ecological products into sources of economic value can help mitigate the tension between environmental conservation and economic growth. Using the capital cycle theory and the unique qualities of eco-friendly items, this study utilizes a case study approach, focusing on Zhengjiabang Village located in Changyang, Hubei Province. Meanwhile, we build a value realization chain of ecological products by combining the practical process of the village. On this basis, we reveal the roles of each subject and object in the evolutionary process, from ecological resources to ecological products. We also identify the key issues of eco-industrial expansion and spatial evolution. Taking the industrialization of ecological capital as the key, we add a step of value feedback to create a cycle of ecological product value realization and strengthen the sustainability of capital and industry. Ultimately, we aim to promote the transformation of ecological environmental advantages into economic advantages, and provide a new concept able to promote the construction of endogenous mechanisms for realizing the value of ecological products in rural areas.

The NONRATT023402.2/rno-miR-3065-5p/NGFR axis affects levodopa-induced dyskinesia in a rat model of Parkinson’s disease

Levodopa-induced dyskinesia (LID) is a common motor complication in Parkinson’s disease. However, few studies have focused on the pathogenesis of LID at the transcriptional level. NONRATT023402.2, a long non-coding RNA (lncRNA) that may be related to LID was discovered in our previous study and characterized in rat models of LID. In the present study, NONRATT023402.2 was overexpressed by injection of adeno-associated virus (AAV) in striatum of LID rats, and 48 potential target genes, including nerve growth factor receptor (NGFR) were screened using next-generation sequencing and target gene predictions. The NONRATT023402.2/rno-miR-3065-5p/NGFR axis was verified using a dual luciferase reporter gene. Overexpression of NONRATT023402.2 significantly increased the abnormal involuntary movements (AIM) score of LID rats, activated the PI3K/Akt signaling pathway, and up-regulated c-Fos in the striatum. NGFR knockdown by injection of ShNGFR-AAV into the striatum of LID rats resulted in a significant decrease in the PI3K/Akt signaling pathway and c-Fos expression. The AIM score of LID rats was positively correlated with the expressions of NONRATT023402.2 and NGFR. A dual luciferase reporter assay showed that c-Fos, as a transcription factor, bound to the NONRATT023402.2 promoter and activated its expression. Together, the results showed that NONRATT023402.2 regulated NGFR expression via a competing endogenous RNA mechanism, which then activated the PI3K/Akt pathway and promoted c-Fos expression. This suggested that c-Fos acted as a transcription factor to activate NONRATT023402.2 expression, and form a positive feedback regulation loop in LID rats, thus, aggravating LID symptoms. NONRATT023402.2 is therefore a possible novel therapeutic target for LID.

Resource interaction in smallholder farms is linked to farm sustainability: evidence from Indian Sundarbans

Efficient resource utilization in small-scale farms is crucial to achieving farm sustainability through endogenous mechanisms. However, the precise mechanisms to integrate farm resources to achieve farm sustainability are not very clear yet. By capturing the interaction among farm resources as a network phenomenon, we aimed to identify the discrete resource interactions (RIs) associated with higher farm sustainability in different farm types of Indian Sundarbans. First, we assessed the sustainability of 140 integrated farms using a synthesized assessment framework. Then, we considered four network motifs, namely linkage (a one-way link between two resources), reciprocal linkage (a two-way link between two resources), triad (three resources having closed interconnectedness), and the presence of a farm resource at the core of a network. Using RI network data of 140 farms and employing a graph theoretic approach we identified discrete network motifs (i.e., resource interaction) associated with highly sustainable farms in different farm types. We found a predominance of rice, vegetables and pond-based integration and identified 32 linkages, 11 reciprocal linkages, 21 triads, and three resources at the network core that occurred and co-occurred on highly sustainable farms, and thus critical to achieving farm sustainability. Further, multivariate analyses established that the properties of RI networks could explain farm sustainability significantly. We anticipate that sustainability in small-scale farms can be achieved by strategically designing new RIs on the farm. However, there may be limitations to such achievement depending on the nature of RI and the type of farm.

The effect of selected aminoglycoside antibiotics on human serum albumin antioxidant activity: a spectroscopic and calorimetric comparative study

BackgroundHuman serum albumin (HSA) is a valuable component of non-enzymatic and endogenous antioxidant mechanisms. The antioxidant activity of HSA can be modulated by ligands, including drugs. Although this is a central topic in the field of oxidation, there is still a lack of information about the protection against the effects of elevated free radical levels.MethodsThe aim of this study was to investigate the antioxidant activity of kanamycin (KAN) and neomycin (NEO) and their effect on the antioxidant potential of HSA using spectroscopic and microcalorimetric techniques.ResultsDespite the fact that kanamycin and neomycin interact with HSA, no changes in the secondary structure of the protein have been observed. The analysis of the aminoglycoside antibiotics showed their low antioxidant activity and a synergistic effect of the interaction, probably due to the influence of ligands (KAN, NEO) on the availability of HSA amino acid residues functional groups, such as the free thiol group (Cys-34).ConclusionsBased on the spectroscopic and microcalorimetric data, both KAN and NEO can be considered modulators of the HSA antioxidant activity.

Astrocytes in stroke-induced neurodegeneration: a timeline.

Stroke is a condition characterized by sudden deprivation of blood flow to a brain region and defined by different post-injury phases, which involve various molecular and cellular cascades. At an early stage during the acute phase, fast initial cell death occurs, followed by inflammation and scarring. This is followed by a sub-acute or recovery phase when endogenous plasticity mechanisms may promote spontaneous recovery, depending on various factors that are yet to be completely understood. At later time points, stroke leads to greater neurodegeneration compared to healthy controls in both clinical and preclinical studies, this is evident during the chronic phase when recovery slows down and neurodegenerative signatures appear. Astrocytes have been studied in the context of ischemic stroke due to their role in glutamate re-uptake, as components of the neurovascular unit, as building blocks of the glial scar, and synaptic plasticity regulators. All these roles render astrocytes interesting, yet understudied players in the context of stroke-induced neurodegeneration. With this review, we provide a summary of previous research, highlight astrocytes as potential therapeutic targets, and formulate questions about the role of astrocytes in the mechanisms during the acute, sub-acute, and chronic post-stroke phases that may lead to neurorestoration or neurodegeneration.

Bioagents Induced Resistance to Ceratocystis fimbriata in Pomegranate

Pomegranate is the most important fruit crop consumed in the world. In India the plant is cultivated in almost all agroecological areas, however, yields remain low due to attacks by various pathogens and insects. Among the pathogens, wilt caused by Ceratocystis fimbriata is an important disease and its soil-borne pathogen is difficult to manage. To contribute to the control of this microbial pathogen, the stimulatory effect of the Pomegranate defense system of bioagents in the pomegranate interaction was evaluated. Resistance-inducing rhizobacteria offer an excellent alternative in providing natural, effective, safe, persistent, and durable protection. Plants have endogenous defense mechanisms that can be induced in response to the pathogen and bio-agents. The increased activities of the defense enzymes, viz. peroxidase (PO), polyphenol oxidase (PPO), phenylalamine ammonia lyase (PAL), and phenolic compounds in the bio-agents treated plants of pomegranate challenged with C. fimbriata were recorded in the present studies. The maximum activity of defense enzymes viz., peroxidase, polyphenol oxidase, phenylalanine ammonia-lyase and total phenol was recorded in diamond (T. viride) followed by T. harzianum (Th-R) and Platinum (P. fluorescens) indicating the role of bio-agents in increasing the role of defense enzymes in suppression of wilt.

Semi-endogenous or fully endogenous growth? A unified theory

Is growth ultimately fully endogenous or semi-endogenous? Three decades of theoretical and empirical growth economics have kept both possibilities open. Here, R&D-driven growth is a general combination of both semi-endogenous and fully endogenous mechanisms.I demonstrate that if the semi-endogenous growth component is indispensable to the actual growth mechanism, the long-run growth rate follows the semi-endogenous growth predictions. Conversely, if the semi-endogenous growth is non-essential and the world population experiences slow growth, the fully endogenous growth mechanism could dictate the long run, even if it is not essential.If no other (third) growth mechanism exists, a criterion sufficient to ascertain the essentiality of semi-endogenous growth is that reduced research consistently leads to fewer innovations.If an unknown third growth engine exists, the steady state remains semi-endogenous, provided the essentiality criterion is met. Regardless of how this third factor impacts short-term growth, semi-endogenous growth will prevail in the long run.

Effects of hsa_circ_0074854 on colorectal cancer progression, construction of a circRNA–miRNA–mRNA network, and analysis of immune infiltration

PurposeCircular RNAs have been demonstrated to be closely associated with the onset and metastasis of colorectal cancer. However, the roles and clinical diagnostic value of most circRNAs in colorectal cancer remain unclear.MethodsWe detected the differential expression of circRNAs in CRC tissues and cells and investigated their relationship in conjunction with clinical pathological features. Additionally, we performed cellular functional experiments in CRC cell lines to explore the functions of circRNAs. To further validate the potential ceRNA network, qPCR was performed to assess the expression of miRNA and mRNA in CRC cells after differential expression of circRNAs knockdown. Furthermore, database analysis was utilized to explore the relationship between the predicted mRNAs and immune infiltration in CRC.ResultsOur research findings indicate a positive correlation between hsa_circ_0074854 expression and advanced clinical pathological features, as well as an unfavorable prognosis. Knockdown of hsa_circ_0074854 was observed to inhibit proliferation and migration capabilities of colorectal cancer cells, affecting the cell cycle progression, and simultaneously promoting apoptosis. A competing endogenous RNA mechanism may exist among circRNAs, miRNAs, and mRNAs. Furthermore, the expression of target genes displayed correlations with the abundance of certain immune cells.ConclusionWe propose a novel ceRNA network and evaluate the interplay between target genes and immune cells, providing novel insights for the diagnosis and targeted therapy of CRC.

The novel angiogenesis regulator circFAM169A promotes the metastasis of colorectal cancer through the angiopoietin-2 signaling axis.

Angiogenesis plays an important role in the metastasis of cancers. However, the mechanisms whereby circular RNAs (circRNAs) regulate angiogenesis and affect cancer metastasis are still unclear. We used gene set variation and Spearman's correlation analyses to identify novel angiogenesis-related circRNAs, including circFAM169A. The Kyoto Encyclopedia of Genes and Genomes and Gene Ontology were used to assess the potential biological function of circFAM169A. A quantitative reverse transcription-PCR (qRT-PCR) analysis of 20 pairs of colorectal cancer (CRC) samples was performed to detect the expression level of circFAM169A. Transwell assays, tube formation assays, and nude mouse metastatic tumor models were used to study the function of circFAM169A in CRC. qRT-PCR, dual-luciferase reporter gene assay, RNA antisense purification assay, and Western blot were performed to analyze the competing endogenous RNA mechanism of circFAM169A in promoting CRC angiogenesis. circFAM169A was highly correlated with the hallmark of angiogenesis in CRC patients. It was up-regulated in liver metastasized CRC patients. circFAM169A overexpression promoted the angiogenesis, migration, and invasion of CRC cells while its down-regulation had the opposite effects. In vivo mouse models further highlighted the pro-metastatic role of circFAM169A in CRC. More importantly, we discovered that circFAM169A enhances the expression of angiopoietin-2 by binding to miR-518a-5p.

Environmental and genetic predictors of human cardiovascular ageing

Cardiovascular ageing is a process that begins early in life and leads to a progressive change in structure and decline in function due to accumulated damage across diverse cell types, tissues and organs contributing to multi-morbidity. Damaging biophysical, metabolic and immunological factors exceed endogenous repair mechanisms resulting in a pro-fibrotic state, cellular senescence and end-organ damage, however the genetic architecture of cardiovascular ageing is not known. Here we use machine learning approaches to quantify cardiovascular age from image-derived traits of vascular function, cardiac motion and myocardial fibrosis, as well as conduction traits from electrocardiograms, in 39,559 participants of UK Biobank. Cardiovascular ageing is found to be significantly associated with common or rare variants in genes regulating sarcomere homeostasis, myocardial immunomodulation, and tissue responses to biophysical stress. Ageing is accelerated by cardiometabolic risk factors and we also identify prescribed medications that are potential modifiers of ageing. Through large-scale modelling of ageing across multiple traits our results reveal insights into the mechanisms driving premature cardiovascular ageing and reveal potential molecular targets to attenuate age-related processes.

Presenting the Secrets: Exploring Endogenous Defense Mechanisms in Chrysanthemums against Aphids

As the second-largest cut flower plant globally and one of the top ten traditional flowers in China, chrysanthemums hold significant economic value, encompassing both ornamental and medicinal applications. However, aphids pose a considerable threat as one of the most critical pests affecting chrysanthemums. These pests not only diminish the ornamental value of chrysanthemums through feeding and reproduction but also transmit numerous plant viruses, causing irreversible damage. This review examines aphids’ feeding and damage patterns as a starting point, highlighting the unique endogenous defense mechanisms that have evolved in chrysanthemums during their continuous struggle against aphids. These mechanisms include constitutive defense and induced defense. In addition, we enumerate aphid-resistance genes that have been reported in chrysanthemums. Furthermore, this paper compares and predicts the aphid-resistance genes of other species based on the published Chrysanthemum nankingense genome, aiming to provide a valuable reference for future research on aphid-resistance genes in chrysanthemums.

Plasma Soluble Glycoprotein VI, Platelet Function, Bleeding, and Ischemic Events in Patients Undergoing Elective Percutaneous Coronary Intervention.

Glycoprotein VI (GPVI) is the major platelet-specific collagen receptor. GPVI shedding with generation of soluble GPVI (sGPVI) is an endogenous feedback mechanism preventing platelet overstimulation. sGPVI has not been investigated in patients with chronic coronary syndrome (CCS) undergoing percutaneous coronary intervention (PCI), especially regarding its potential value as a predictor of ischemic and bleeding risk. Baseline plasma sGPVI levels were available in 318 patients with CCS undergoing PCI. Platelet function was assessed by measuring both adenosine diphosphate (ADP) and collagen-induced platelet aggregation. Co-primary endpoints were a composite of death or myocardial injury at 48 hours after PCI, and Bleeding Academic Research Consortium (BARC) type 1 to 5 bleeding at 30 days. There was no significant correlation between sGPVI and platelet function at baseline or at 48 hours after PCI and loading with antiplatelet drugs. Baseline plasma sGPVI levels were not associated with the ischemic risk: the incidence of the ischemic endpoint was 25.0% in the lower, 22.9% in the middle, and 26.7% in the upper sGPVI tertile (p = 0.82). There was a significant nonlinear relationship between sGPVI and the risk of bleeding: the incidence of the bleeding endpoint was 11.8% in the lower, 12.6% in the middle, and 26.4% in the upper sGPVI tertile (p = 0.006). In patients with CCS undergoing PCI, plasma levels of sGPVI did not correlate with ADP- or collagen-induced platelet aggregation. Patients with higher baseline levels of sGPVI may carry an increased risk of bleeding at 30 days after PCI but no excess risk of ischemic events.

Modelling agricultural innovations as a social-ecological phenomenon

Agricultural innovations involve both social and social-ecological dynamics where outcomes emerge from interactions of innovation actors embedded within their ecological environments. Neglecting the interconnected nature of social-ecological innovations can lead to a flawed understanding and assessment of innovations. In this paper, we present an empirically informed, stylized agent-based model of agricultural innovation systems in Mali, West Africa. The study aimed to understand the emergence of food security and income inequality outcomes through two distinct model structures: top-down, aid-driven (exogenous) innovation and bottom-up, community-driven (endogenous) innovation. Our research questions were: i) How does the inclusion of social-ecological interactions in the model affect food security and income inequality outcomes? ii) How do exogenous and endogenous mechanisms influence food insecurity and income inequality? iii) What are the conditions under which exogenous and endogenous mechanisms would improve food security? The structural design of the model was based on a combination of theory, empirics, and mapping of social-ecological dynamics within innovation systems. Using the Social-Ecological Action Situation framework, we mapped the social, social-ecological, and ecological interactions that jointly produce food security outcomes. The exploratory model analysis reveals three key insights: i) Incorporation of social-ecological interactions influences model outcomes. Scenarios with social-ecological interactions showed a stronger relationship between income inequality and food security, lower levels of food security, and higher levels of income inequality than scenarios with social interactions. ii) Endogenous mechanism leads to higher food security and income inequality than the exogenous mechanism. iii) Bidirectional outreach is more effective than unidirectional outreach in improving food security. Inclusion of social-ecological dynamics and interactions such as the role of climate risk perception, social learning and formation of innovation beliefs and desires is key for modelling and analysis of agricultural innovations.

Differential Effects of Thermal Stimuli in Eliciting Temporal Contrast Enhancement: A Psychophysical Study

Offset analgesia (OA) is observed when pain relief is disproportional to the reduction of noxious input and is based on temporal contrast enhancement (TCE). This phenomenon is believed to reflect the function of the inhibitory pain modulatory system. However, the mechanisms contributing to this phenomenon remain poorly understood, with previous research focusing primarily on painful stimuli and not generalizing to nonpainful stimuli. Therefore, the aim of this study was to investigate whether TCE can be induced by noxious as well as innocuous heat and cold stimuli. Asymptomatic subjects (n = 50) were recruited to participate in 2 consecutive experiments. In the first pilot study (n = 17), the parameters of noxious and innocuous heat and cold stimuli were investigated in order to implement them in the main study. In the second (main) experiment, subjects (n = 33) participated in TCE paradigms consisting of 4 different modalities, including noxious heat (NH), innocuous heat (IH), noxious cold (NC), and innocuous cold (IC). The intensity of the sensations of each thermal modality was assessed using an electronic visual analog scale. TCE was confirmed for NH (P < .001), NC (P = .034), and IC (P = .002). Conversely, TCE could not be shown for IH (P = 1.00). No significant correlation between TCE modalities was found (r < .3, P > .05). The results suggest that TCE can be induced by both painful and nonpainful thermal stimulation but not by innocuous warm temperature. The exact underlying mechanisms need to be clarified. However, among other potential mechanisms, this may be explained by a thermo-specific activation of C-fiber afferents by IH and of A-fiber afferents by IC, suggesting the involvement of A-fibers rather than C-fibers in TCE. More research is needed to confirm a peripheral influence. PerspectiveThis psychophysical study presents the observation of temporal contrast enhancement during NH, NC, and innocuous cold stimuli but not during stimulation with innocuous warm temperatures in healthy volunteers. A better understanding of endogenous pain modulation mechanisms might be helpful in explaining the underlying aspects of pain disorders.

Revisiting the puzzle of endogenous nuclear proliferation

Nuclear proliferation literature typically differentiates supply-side and demand-side factors influencing the spread of nuclear weapons. These distinct approaches to the proliferation puzzle raise the following empirical questions: Does nuclear supply stimulate states’ demand for nuclear weapons? Conversely, does the demand for nuclear weapons really facilitate the acquisition of nuclear supply? If such endogeneity exists between the demand-side and supply-side determinants, how would it cause empirical bias in the estimation of their effects on nuclear proliferation? This article aims to unpack endogenous mechanisms of nuclear demand and nuclear supply over the course of nuclear proliferation. In particular, it examines two potential sources of endogeneity: (1) simultaneous interactions between states’ nuclear development decisions and nuclear technological capability and (2) selection bias in nuclear development. To address each source of endogeneity, simultaneous equation models and the duration models with selection are estimated, respectively. Contrary to what recent supply-side literature suggests, the empirical analyses reveal that states’ nuclear demand is primarily driven by external security threats instead of their existing nuclear technology, and that their successful acquisition of nuclear technology mainly follows as the result of nuclear development efforts but does not necessarily depend on individual supply-side factors. This article addresses the typical inference issues in nuclear proliferation research and contributes to our synthetic understanding of proliferation mechanisms.

"Outside-to-inside," "inside-to-outside," and "intrinsic" endogenous pathogenic mechanisms in atopic dermatitis: keratinocytes as the key functional cells involved in both permeability barrier dysfunction and immunological alterations.

Permeability barrier disruption has been shown to induce immunological alterations (i.e., an "outside-to-inside" pathogenic mechanism). Conversely, several inflammatory and immunological mechanisms reportedly interrupt permeability barrier homeostasis (i.e., an "inside-to-outside" pathogenic mechanism). It is now widely recognized that alterations of even a single molecule in keratinocytes can lead to not only permeability barrier dysfunction but also to immunological alterations. Such a simultaneous, bidirectional functional change by keratinocytes is herein named an "intrinsic" pathogenic mechanism. Molecules and/or pathways involved in this mechanism could be important not only as factors in disease pathogenesis but also as potential therapeutic targets for inflammatory cutaneous diseases, such as atopic dermatitis, psoriasis, and prurigo nodularis. Elevation of skin surface pH following permeability barrier abrogation comprises one of the key pathogenic phenomena of the "outside-to-inside" mechanism. Not only type 2 cytokines (e.g., IL-4, IL-13, IL-31) but also type 1 (e.g. IFN-γ), and type 3 (e.g., IL-17, IL-22) as well as several other inflammatory factors (e.g. histamine) can disrupt permeability barrier homeostasis and are all considered part of the "inside-to-outside" mechanism. Finally, examples of molecules relevant to the "intrinsic" pathogenic mechanism include keratin 1, filaggrin, and peroxisome proliferator-activated receptor-α (PPARα).

Exiting the periphery: Possible pathways towards a socio‐economic and institutional de‐marginalization of places

AbstractWhat are the economic, social and institutional mechanisms that make it possible for peripheral areas to regain centrality? To address this issue, this paper takes stock of the current scientific debate on peripheries. Our reasoning is based on a general assumption according to which simple geographic features do not determine per se socio–spatial divisions. Peripheral areas are not natural. By contrast, they are the outcomes of more or less intentional processes that imply hierarchical and power relationships, unequal allocation of economic resources, and reliance upon relational patterns and social norms. Therefore, it is essential to observe how and whether multidimensional socio‐economic changes occur within peripheral areas, deconstructing their marginality. In this regard, this paper highlights four main endogenous mechanisms upon which a de‐marginalization process may rely: (1) transformation in the features of the local institutional make‐up; (2) emergence of collective actions and ‘self‐governance’ processes at the local level; (3) renovation of elite groups; and (4) establishing economic renewal and innovation.