Chronic granulomatous disease (CGD) primarily results from inherited defects in components of the nicotinamide adenine dinucleotide phosphate oxidase enzyme complex. These include gene defects in cytochrome B-245/558 subunit α/β and neutrophil cytosolic factors 1, 2, and 4. Recently, homozygous loss-of-function variants in cytochrome B-245 chaperone 1 gene (CYBC1) have been discovered to cause CGD (CYBC1-CGD). Data on variant-proven CGD from low-income countries, the most underprivileged regions of the world, remain sparse due to numerous constraints. Herein, we report the first cohort of patients with CGD from Nepal, a low-income country in the Himalayas\' challenging terrain. Our report includes a description of a new case of CYBC1 deficiency who was first diagnosed with CGD at our center. Only a dozen cases of CYBC1-CGD have been described in the literature thus far which have been reviewed comprehensively herein. Most of these patients have had significant infections and autoimmune/inflammatory manifestations. Pulmonary and invasive/disseminated bacterial/fungal infections were the most common followed by skin and soft-tissue infections. Inflammatory bowel disease (IBD) was the most common inflammatory manifestation (median age at diagnosis: 9 years) followed by episodes of recurrent/prolonged fever. Other autoimmune/inflammatory manifestations reported in CYBC1-CGD include acute pancreatitis, hemophagocytic lymphohistiocytosis, systemic granulomatosis, interstitial lung disease, arthritis, autoimmune hemolytic anemia, uveitis, nephritis, and eczema. Our analysis shows that patients with CYBC1-CGD are at a significantly higher risk of IBD-like illness as compared to other forms of CGD which merits further confirmatory studies in the future.

The chaperone protein EROS (\"Essential for Reactive Oxygen Species\") was recently discovered in phagocytes. EROS was shown to regulate the abundance of the ROS-producing enzyme NADPH oxidase isoform 2 (NOX2) and to control ROS-mediated cell killing. Reactive oxygen species are important not only in immune surveillance, but also modulate physiological signaling responses in multiple tissues. The roles of EROS have not been previously explored in the context of oxidant-modulated cell signaling. Here we show that EROS plays a key role in ROS-dependent signal transduction in vascular endothelial cells. We used siRNA-mediated knockdown and developed CRISPR/Cas9 knockout of EROS in human umbilical vein endothelial cells (HUVEC), both of which cause a significant decrease in the abundance of NOX2 protein, associated with a marked decrease in RAC1, a small G protein that activates NOX2. Loss of EROS also attenuates receptor-mediated hydrogen peroxide (H2O2) and Ca2+ signaling, disrupts cytoskeleton organization, decreases cell migration, and promotes cellular senescence. EROS knockdown blocks agonist-modulated eNOS phosphorylation and nitric oxide (NO●) generation. These effects of EROS knockdown are strikingly similar to the alterations in endothelial cell responses that we previously observed following RAC1 knockdown. Proteomic analyses following EROS or RAC1 knockdown in endothelial cells showed that reduced abundance of these two distinct proteins led to largely overlapping effects on endothelial biological processes, including oxidoreductase, protein phosphorylation, and endothelial nitric oxide synthase (eNOS) pathways. These studies demonstrate that EROS plays a central role in oxidant-modulated endothelial cell signaling by modulating NOX2 and RAC1.

Essential for reactive oxygen species (EROS) protein is a recently identified molecular chaperone of NOX2 (gp91phox), the catalytic subunit of phagocyte NADPH oxidase. Deficiency in EROS is a recently identified cause for chronic granulomatous disease, a genetic disorder with recurrent bacterial and fungal infections. Here, we report a cryo-EM structure of the EROS-NOX2-p22phox heterotrimeric complex at an overall resolution of 3.56Å. EROS and p22phox are situated on the opposite sides of NOX2, and there is no direct contact between them. EROS associates with NOX2 through two antiparallel transmembrane (TM) α-helices and multiple β-strands that form hydrogen bonds with the cytoplasmic domain of NOX2. EROS binding induces a 79° upward bend of TM2 and a 48° backward rotation of the lower part of TM6 in NOX2, resulting in an increase in the distance between the two hemes and a shift of the binding site for flavin adenine dinucleotide (FAD). These conformational changes are expected to compromise superoxide production by NOX2, suggesting that the EROS-bound NOX2 is in a protected state against activation. Phorbol myristate acetate, an activator of NOX2 in vitro, is able to induce dissociation of NOX2 from EROS with concurrent increase in FAD binding and superoxide production in a transfected COS-7 model. In differentiated neutrophil-like HL-60, the majority of NOX2 on the cell surface is dissociated with EROS. Further studies are required to delineate how EROS dissociates from NOX2 during its transport to cell surface, which may be a potential mechanism for regulation of NOX2 activation.

After every school shooting in the United States both a wish and a fear arise: Will this be the one? Will this be the tipping point for change in a nation so deeply divided over the meaning of \"the right to bear arms?\" Sandy Hook, Connecticut? No. Parkland, Florida? No. So, why might the killing of 19 children and 2 teachers in Uvalde, Texas, prove different? The American epidemic of mass school shootings betrays a country\'s willingness to let its children disappear, to sacrifice them on the altar of an archetypally violent ethos. While the internal experiences of alienation, resentment and contempt are often at play in the individuals who carry out such violence, the author suggests that the uniquely American glorification of \"the lone wolf\", the \"rugged individual\" and the \"misunderstood hero\" fuels a supportive background for mass shooters in a nation that appears to be enamoured of ancient patriarchal attitudes as it doubles down on its valuing of weaponry. Such patriarchal attitudes, underscored by capitalism and the profits of the gun industry, are implicated in the territorial adhesion to American gun rights and in the high cost paid by the blood of innocents. Drawing on Vestergaard & Odde\'s (2021) concepts of socio-analysis and sociality, this paper explores the dynamic process of \"mass-character\" marked by \"contagion, imitation, attraction and repulsion\" that convolute cultural values of heritage and freedom into the perverse expression of mass violence.
Aux États‐Unis, après chaque fusillade dans une école, un souhait et une crainte surgissent à la fois : est‐ce que celle‐ci fera une différence? Marquera‐t‐elle le point de basculement d\'un changement dans une nation si profondément divisée sur la signification du « droit de porter des armes »? Sandy Hook, dans le Connecticut? Non. Santa Fe, au Texas? Non. Alors, pourquoi l’assassinat de 19 enfants et de 2 enseignants à Uvalde, au Texas, pourrait‐il s\'avérer différent? L\'épidémie américaine de fusillades de masse dans les écoles trahit la volonté d\'un pays de laisser ses enfants disparaître, de les sacrifier sur l\'autel d\'une philosophe archétypale de la violence. Alors que les expériences internes d\'aliénation, de ressentiment et de mépris sont souvent en jeu chez les individus qui commettent de telles violences, l\'auteur suggère que la glorification typiquement américaine du « loup solitaire », de « l\'individu robuste » et du « héros incompris » alimente un arrière‐plan favorable aux tireurs de masse. Ceci dans une nation qui semble éprise d’anciennes attitudes patriarcales et qui persiste et signe concernant son attachement pour les armes. De telles attitudes patriarcales, soulignées par le capitalisme et les profits de l\'industrie des armes à feu, sont impliquées dans l\'adhésion territoriale aux droits américains sur les armes à feu et dans le coût élevé payé par le sang d\'innocents. S\'appuyant sur les concepts de socioanalyse et de socialité de Vestergaard et Odde (2021), cet article explore le processus dynamique du « caractère de masse » marqué par « la contagion, l\'imitation, l\'attrait et la répulsion » qui tournent les valeurs culturelles liées au patrimoine et à la liberté en une expression perverse de violence de masse.
Nach jeder Schießerei in einer Schule in den Vereinigten Staaten entsteht sowohl ein Wunsch als auch eine Angst: Wird dies der eine Fall sein? Wird dies der Wendepunkt für einen Wandel in einer Nation sein, die so tief über die Bedeutung des “Rechts, Waffen zu tragen” gespalten ist? Sandy Hook, Connecticut? Nein. Santa Fe, Texas? Nein. Warum könnte sich die Ermordung von 19 Kindern und 2 Lehrern in Uvalde, Texas, als etwas anderes herausstellen? Die amerikanische Epidemie von Massenschießereien an Schulen verrät die Bereitschaft eines Landes, seine Kinder verschwinden zu lassen und sie auf dem Altar eines archetypischen Gewaltethos zu opfern. In Anbetracht dessen, daß die inneren Erfahrungen der Entfremdung, des Grolls und der Verachtung bei den Personen, die solche Gewalt ausüben, oft eine Rolle spielen, schlägt der Autor vor, daß die typisch amerikanische Verherrlichung des “einsamen Wolfes”, des “schroffen Individuums” und des “mißverstandenen Helden” den Treibstoff liefert zu einem unterstützenden Hintergrund für Massenschützen in einer Nation, die anscheinend von alten patriarchalischen Einstellungen fasziniert ist und gleichzeitig die Wertschätzung von Waffen verdoppelt. Solche patriarchalischen Einstellungen, die durch den Kapitalismus und die Profite der Waffenindustrie unterstützt werden, sind mit der territorialen Aufrechterhaltung der amerikanischen Waffenrechte und den hohen Kosten verbunden, die durch das Blut Unschuldiger gezahlt werden. Basierend auf den Konzepten der Sozioanalyse und Sozialität von Vestergaard & Odde (2021) untersucht dieser Artikel den dynamischen Prozeß des “Massencharakters”, der durch “Ansteckung, Nachahmung, Anziehung und Abstoßung” gekennzeichnet ist und kulturelle Werte wie Tradition und Freiheit in einen perversen Ausdruck von Massengewalt verdreht.
Dopo ogni sparatoria nelle scuole degli Stati Uniti sorgono sia un desiderio che una paura: sarà questa la volta buona? Sarà questo il punto di svolta per il cambiamento di una nazione così profondamente divisa sul significato del ‘diritto di portare le armi’? Sandy Hook, Connecticut? No. Santa Fe, Texas? No. Quindi, perché l’uccisione di 19 bambini e 2 insegnanti ad Uvalde, Texas, potrebbe essere diversa? L’epidemia americana delle sparatorie di massa nelle scuole tradisce la volontà di un paese di lasciar scomparire i propri figli, di sacrificarli all’altare di un ethos archetipicamente violento. Mentre le esperienze interne di alienazione, risentimento e disprezzo sono spesso in gioco negli individui che compiono tale violenza, l’Autrice suggerisce che la glorificazione tipicamente americana del ‘lupo solitario’ e dell’eroe incompreso alimenta un sostegno per gli omicidi di massa in una nazione che sembra essere innamorata di antichi atteggiamenti patriarcali, mentre raddoppia il valore delle armi. Tali atteggiamenti patriarcali, sottolineati dal capitalismo e dai profitti dell’industria delle armi, sono implicati nell’adesione territoriale al diritto americano sulle armi e nell’alto costo pagato dal sangue degli innocenti. Basandosi sui concetti di socio‐analisi e socialità di Vestergaard e Odde (2021), questo articolo esplora il processo dinamico del ‘carattere di massa’, dove ‘contagio, imitazione, attrazione e repulsione’ trasformano i valori culturali del patrimonio e della libertà nell’espressione perversa della violenza di massa.
После каждого случая стрельбы в школах в Соединенных Штатах вместе со страхом возникает желание, чтобы этот случай оказался тем самым событием, переломной точкой в направлении перемен в стране со столь глубоким расколом в отношении “права на ношение оружия”. Сэнди Хук, штат Коннектикут? Нет. Санта‐Фе, Техас? Нет. Почему тогда убийство девятнадцати детей и двух учителей в Ювалде в штате Техас может стать особым случаем? Американская эпидемия массовых убийств в школах свидетельствует о готовности страны позволить своим детям исчезнуть, принести их в жертву на алтарь архетипически жестокого этоса. Очевидно, что люди, совершающие такое преступление, часто охвачены внутренними переживаниями отчуждения, обиды и презрения, но вместе с тем автор предполагает, что благоприятную основу для массовых убийств создается чисто американским восхвалением “одинокого волка”, “ярко выраженной индивидуальности” и “непонятого героя”, что усиливает ценность оружия для нации, очарованной, по всей видимости, древними патриархальными установками. Патриархальные установки, базирующиеся на капитализме и прибыльности оружейной индустрии, составляют неотъемлемую часть территориальной приверженности американскому праву на ношение оружия и той высокой цены, которую приходится платить за кровь невинных. Опираясь на концепцию социоанализа и социальности Вестергора и Одде (2021), автор данной статьи исследует динамичный процесс “массовых явлений” со свойственными им “заражением, подражанием, притяжением и отталкиванием”, которые превращают культурные ценности преемственности и свободы в извращенное выражение массового насилия.
Después de cada tiroteo en un colegio de Estados Unidos surge un deseo y un temor: ¿será éste? ¿Será éste el punto de inflexión para el cambio en una nación tan profundamente dividida sobre el significado del “derecho a portar armas”? ¿Sandy Hook, Connecticut? No. ¿Santa Fe, Texas? No. Entonces, ¿por qué la matanza de 19 niños y 2 profesores en Uvalde, Texas, podría ser diferente? La epidemia estadounidense de tiroteos masivos en escuelas revela la voluntad de un país de dejar desaparecer a sus niños, de sacrificarlos en el altar de un ethos arquetípicamente violento. Aunque las experiencias internas de alienación, resentimiento y desprecio suelen ponerse en juego en los individuos que llevan a cabo este tipo de violencia, la autora sugiere que la glorificación exclusivamente estadounidense del “lobo solitario”, el “individuo rudo” y el “héroe incomprendido” alimenta un trasfondo de sostén para los autores de tiroteos masivos, en una nación que parece estar enamorada de antiguas actitudes patriarcales mientras redobla su valoración del armamento. Dichas actitudes patriarcales, acentuadas por el capitalismo y los beneficios de la industria armamentística, están implicadas en la adhesión territorial al derecho estadounidense a las armas y en el alto costo pagado por la sangre de inocentes. Basándose en los conceptos de socioanálisis y socialidad de Vestergaard y Odde (2021), este artículo explora el proceso dinámico del “carácter de masas”, marcado por el “contagio, la imitación, la atracción y la repulsión”, que convierte los valores culturales del patrimonio y la libertad en la expresión perversa de la violencia de masas.
乌瓦尔德的一些事:美国父权制与对无辜者的屠杀 每当美国发生校园枪击案后, 人们都会产生一种愿望和恐惧:这次会是变革的转折点吗?在关于 \"持枪权 \"含义存在如此大的分歧的国家, 这会是变革的转折点吗?在康涅狄格州的桑迪胡克会是转折点吗?不是。在得克萨斯州的圣达菲会是吗?不是。那么, 凭什么, 发生在德克萨斯州乌瓦尔德的 19 名儿童和 2 名教师被杀事件, 会证明与以往有所不同呢?美国大规模校园枪击案的流行暴露了一个国家意愿, 即其愿意让自己的孩子消失, 愿意把他们牺牲在原型性的暴力精神的祭坛上。虽然, 实施此类暴力的个人身上存在着疏远、怨恨和蔑视的内心体验, 但作者认为, 美国独有的对 “独狼”、“粗犷的个人”和对 “被误解的英雄”的美化, 为大规模枪杀者提供了支持性背景, 而这个国家在加倍重视武器装备的同时, 似乎还迷恋着古老的父权态度。这种由资本主义和枪支工业利润所支撑父权态度, 牵连着地域性的美国枪支权利, 并由无辜者的鲜血为此付出高昂的代价。本文借鉴维斯特加德和奥德 (Vestergaard & Odde, 2021 年)的社会分析和社会性概念, 探讨了“大众的”动力过程, 这一过程以“传染、模仿、吸引和排斥”为特征, 并将传统和自由的文化价值观扭曲为大规模暴力的反常表现形式。.

In the introduction to The Psychology of the Transference (1946), Carl Jung sketched out a theory of \"erotic phenomenology\" which condenses his teaching about sexuality and romantic love into a very concise summary. But the meaning of this passage is obscured in the English translation given in the Collected Works of C. G. Jung. I propose here a new translation which makes Jung\'s meaning clearer, along with a commentary which explains it in the context of Freudian drive theory and German 19th century philosophy. Invoking the concepts of instinct, mind, and Eros (both the passion and the divine figure), Jung\'s theory says that male sexual desire can be cultivated or repressed in four distinct ways, each associated with a female symbolic figure or anima image: Eve, Helen, Mary and Sophia.
Dans son introduction à La Psychologie du Transfert (1946), Carl Jung esquisse une « phénoménologie érotique » qui condense ses enseignements sur la sexualité et le désir en un résumé très concis. Mais le sens de ce passage est brouillé dans la traduction anglaise des Collected Works of C.G. Jung. Je propose ici une nouvelle traduction qui rend l\'argument de Jung plus clair, suivie d\'un commentaire qui l\'explique dans le contexte de la théorie freudienne des pulsions et de la philosophie allemande du XIXe siècle. Invoquant les concepts d\'instinct, d\'esprit et d\'Eros (en tant que passion ainsi que figure divine), la théorie de Jung dit que le désir sexuel masculin peut être cultivé ou réprimé de quatre manières distinctes, chacune associée à une figure symbolique féminine ou image de l\'anima: Eve, Hélène, Marie et Sophia.
In der Einleitung zu Die Psychologie der Uebertragung (1946) skizzierte Carl Jung eine «erotischen Phänomenologie», die seine Lehren über Sexualität und romantische Liebe in einer sehr prägnanten Zusammenfassung umreißt. Aber die Bedeutung dieser Passage ist in der englischen Übersetzung in den Collected Works of C.G. Jung unklar. Ich schlage hier eine neue Übersetzung vor, die Jungs Bedeutung klarer macht, zusammen mit einem Kommentar, der sie im Kontext der Freudschen Triebtheorie und der deutschen Philosophie des 19. Jahrhunderts erklärt. Unter Berufung auf die Konzepte des Instinkts und Triebe, des Geistes und des Eros (sowohl der Leidenschaft als auch der göttlichen Figur) besagt Jungs Theorie, daß männliches sexuelles Verlangen auf vier verschiedene Arten kultiviert oder unterdrückt werden kann, die jeweils mit einer weiblichen Symbolfigur oder einem Animabild verbunden sind: Eva, Helena, Maria und Sophia.
Nell\'introduzione a La Psicologia del Transfert (1946), Carl Jung abbozza una “fenomenologia erotica” in cui condensa in una sintesi concisa il suo insegnamento sulla sessualità e il desiderio. Ma il significato di questo passaggio non e chiaro nella traduzione inglese delle Collected Works of C. G. Jung. Propongo qui una nuova traduzione che renda più chiaro il significato di Jung, seguito da un commento che lo spiega nel contesto della teoria freudiana delle pulsioni e della filosofia tedesca del XIX secolo. Riferendosi ai concetti d\'istinto, mente ed Eros (intendendo sia la passione che la figura divina), la teoria di Jung afferma che il desiderio sessuale maschile può essere coltivato o represso in quattro modi distinti, ciascuno associato a una figura simbolica femminile o immagine dell\'Anima: Eva, Elena, Maria e Sofia.
Во введении к книге «Психология переноса» (1946 г.) Карл Юнг приводит «феноменологии эроса», которая является кратким изложением его учения о сексуальности и желании. Однако в английском переводе Собрания сочинений К. Г. Юнга смысл этого фрагмента неясен. Я предлагаю здесь новый перевод, который проясняет, что имел в виду Юнг, а также привожу комментарий, объясняющий его идею в контексте фрейдистской теории влечений и немецкой философии XIX века. Юнг в своей теории обращается к понятиям инстинкт, дуx и Эрос (и как страсть, и как образ божества) и полагает, что мужское сексуальное желание может культивироваться либо подавляться четырьмя различными способами, каждый из которых связан с женской символической фигурой, или образом Анимы: Евой, Еленой, Марией и Софией.
En la introducción a La Psicología de la Transferencia (1946), Carl Jung esbozó una “fenomenología erótica” que condensa sus enseñanzas sobre la sexualidad y el amor romántico en un resumen muy conciso. Pero el significado de este pasaje queda opacado en la traducción inglesa de las Obras Completas de C.G. Jung. Propongo aquí una nueva traducción que aclara el significado de Jung, junto con un comentario que lo explica en el contexto de la teoría freudiana de la pulsión y la filosofía alemana del siglo XIX. Invocando los conceptos de instinto, mente y Eros (tanto la pasión como la figura divina), la teoría de Jung expresa que el deseo sexual masculino puede cultivarse o reprimirse de cuatro maneras distintas, cada una asociada a una figura simbólica femenina o imagen del ánima: Eva, Helena, María y Sofía.
荣格的情色现象学 在《移情心理学》(1946), 的序言中, 荣格勾勒了一个“情色现象学”, 这一描绘把他关于性与浪漫之爱的教学内容浓缩为一个极为简约的概述。但这一段落的含义被淹没于荣格全集的英译版中。在此我提供了一个新的翻译, 从而让荣格的意思更加明晰, 而后跟随了一个对此的评论, 这一评论基于弗洛伊德驱力理论和19世纪德国哲学的背景, 来对这一段落进行了解释。荣格的理论使用了 本能, 心理, 艾诺斯 (激情与神性的角色)这些概念, 来说明男性的性欲望可以被以四种方式培育或压抑, 每一种方式都关联着一种女性象征角色或阿尼玛意象:夏娃, 海伦, 玛丽和索菲亚。.

UNASSIGNED: Perceived benefits are considered one of the significant factors affecting an individual\'s decision-making process. Our study aimed to explore the influence mechanism of perceived benefits in the decision-making process of unsafe behaviors.
UNASSIGNED: Our study used the \"One Stimulus-Two Key Choice (S-K1/K2)\" paradigm to conduct an EEG experiment. Participants (N = 18) made decisions in risky scenarios under high perceived benefits (HPB), low perceived benefits (LPB), and control conditions (CC). Time domain analysis and time-frequency analysis were applied to the recorded EEG data to extract ERPs (event-related potentials) and EROs (event-related oscillations), which include the P3 component, theta oscillations, alpha oscillations, and beta oscillations.
UNASSIGNED: Under the HPB condition, the theta power in the central (p = 0.016*) and occipital regions (p = 0.006**) was significantly decreased compared to the CC. Similarly, the alpha power in the frontal (p = 0.022*), central (p = 0.037*), and occipital regions (p = 0.014*) was significantly reduced compared to the CC. Under the LPB condition, theta power in the frontal (p = 0.026*), central (p = 0.028*), and occipital regions (p = 0.010*) was significantly reduced compared to the CC. Conversely, alpha power in the frontal (p = 0.009**), central (p = 0.012*), and occipital regions (p = 0.040*) was significantly increased compared to the HPB condition.
UNASSIGNED: The high perceived benefits may reduce individuals\' internal attention and evoke individuals\' positive emotions and motivation, leading individuals to underestimate risks. Consequently, they exhibited a greater inclination toward unsafe behaviors. However, the low perceived benefits may reduce individuals\' memory review, resulting in a simple decision-making process, and they are more inclined to make fast decisions to avoid loss. The research results can help to provide targeted intervention measures, which are beneficial to reducing workers\' unsafe behaviors.

The tomato crop is very sensitive to stress conditions. A water deficit is defined as when precipitation is less than the evapotranspiration (ETc) of the crop in a given period, and in this scenario of climate change, it is identified as responsible for global productivity losses. The use of potential technologies for better irrigation management, such as electromagnetically treated water, remains controversial. Thus, the objective of the present work was to investigate the effects of very low-frequency electromagnetic resonance field treatment on water for tomato crops submitted to different irrigation rates. For this, an experiment was carried out under controlled conditions with different types of water: electromagnetically treated water (WTVLF) and untreated water (UNW), as well as four water replacement rates: 40, 60, 80, and 100% ETc. The electromagnetic treatment of the water was carried out using the commercial equipment AQUA4D®. The experiment was carried out in pots with five replications per treatment. Lower activity of SOD, POD, CAT, and APX enzymes was observed in plants irrigated with water treated with very low-frequency electromagnetic resonance fields (WTVLF), indicating less oxidative stress caused by water deficit. Water deficit reduced chlorophyll content, but the effects were less harmful with WTVLF water. The water deficit resulted in less accumulation of dry matter and less productivity in a linear relationship. However, plants irrigated with WTVLF showed increments of about 20% in dry matter accumulation and 20% in fruit production concerning plants irrigated with untreated water, independent of the irrigation rates. We can conclude that irrigation with WTVLF can be a solution to reduce the damage caused by water deficits and increase the productivity of tomato crops.

Chronic Granulomatous Disease (CGD) is an inborn error of immunity characterised by opportunistic infection and sterile granulomatous inflammation. CGD is caused by a failure of reactive oxygen species (ROS) production by the phagocyte NADPH oxidase. Mutations in the genes encoding phagocyte NADPH oxidase subunits cause CGD. We and others have described a novel form of CGD (CGD5) secondary to lack of EROS (CYBC1), a highly selective chaperone for gp91phox. EROS-deficient cells express minimal levels of gp91phox and its binding partner p22phox, but EROS also controls the expression of other proteins such as P2X7. The full nature of CGD5 is currently unknown. We describe a homozygous frameshift mutation in CYBC1 leading to CGD. Individuals who are heterozygous for this mutation are found in South Asian populations (allele frequency = 0.00006545), thus it is not a private mutation. Therefore, it is likely to be the underlying cause of other cases of CGD.

High concentration of extracellular ATP acts as a danger signal that is sensed by the P2X7 receptor (P2X7R). This ATP-gated ion channel has been shown to induce multiple metabotropic events such as changes in plasma membrane composition and morphology, ectodomain shedding, activation of lipases, kinases, and transcription factors as well as cytokine release. The specific signaling pathways and molecular mechanisms remain largely obscure. Using an unbiased genome-scale CRISPR/Cas9 screening approach in a murine T cell line, Ryoden et al. (2022, 2020) identified three proteins involved in P2X7 regulation and signaling: Essential for Reactive Oxygen Species (EROS) is essential for P2X7 folding and maturation, and Xk and Vsp13a are required for P2X7-mediated phosphatidyl serine exposure and cell lysis. They further provide evidence for an interaction of Xk and Vsp13a at the plasma membrane and confirm the role of Xk in ATP-induced cytolysis in primary CD25+CD4+ T cells from Xk-/- mice.

The nucleocapsid protein of the SARS-CoV-2 virus comprises two RNA-binding domains and three regions that are intrinsically disordered. While the structures of the RNA-binding domains have been solved using protein crystallography and NMR, current knowledge of the conformations of the full-length nucleocapsid protein is rather limited. To fill in this knowledge gap, we combined coarse-grained molecular simulations with data from small-angle X-ray scattering (SAXS) experiments using the ensemble refinement of SAXS (EROS) method. Our results show that the dimer of the full-length nucleocapsid protein exhibits large conformational fluctuations with its radius of gyration ranging from about 4 to 8 nm. The RNA-binding domains do not make direct contacts. The disordered region that links these two domains comprises a hydrophobic α-helix which makes frequent and nonspecific contacts with the RNA-binding domains. Each of the intrinsically disordered regions adopts conformations that are locally compact, yet on average, much more extended than Gaussian chains of equivalent lengths. We offer a detailed picture of the conformational ensemble of the nucleocapsid protein dimer under near-physiological conditions, which will be important for understanding the nucleocapsid assembly process.