In the article, “Cooperativity of E‐prostanoid receptor subtypes in regulating signaling and growth inhibition in human airway smooth muscle” by James V. Michael, Adelina Gavrila, Ajay P. Nayak, Tonio Pera, Jennifer R. Liberato, Steven R. Polischak, Sushrut D. Shah, Deepak A. Deshpande, and Raymond B. Penn, in FASEB J. April 2019 33:4780–4789 (doi: 10.1096/fj.201801959R), there is an error in Figure

Lung ischemia‐reperfusion (IR) injury is a common clinical pathology associated with high mortality. Ferroptosis, a novel mode of cell death elicited by iron‐dependent phospholipid peroxidation, has been implicated in ischemic events. Acyl‐CoA synthetase long‐chain family member 4 (ACSL4) is one of the main enzymes in pro‐ferroptotic lipid metabolism. In this study, the involvement of ferroptotic death

Focal and segmental glomerulosclerosis (FSGS) is a histological pattern frequently found in patients with nephrotic syndrome that often progress to end‐stage kidney disease. The initial step in development of this histologically defined entity is injury and ultimately depletion of podocytes, highly arborized interdigitating cells on the glomerular capillaries with important function for the glomerular

Our previous research revealed that steroid receptor coactivators (Src)‐1 and ‐2 serve a critical cooperative role in production of parturition signals, surfactant protein A and platelet‐activating factor, by the developing mouse fetal lung (MFL). To identify the global landscape of genes in MFL affected by Src‐1/‐2 double‐deficiency, we conducted RNA‐seq analysis of lungs from 18.5 days post‐coitum

Polyphyllin I (PPI) is a natural phytochemical drug isolated from plants which can inhibit the proliferation of cancer cells. One of the PPI tumor‐inhibitory effects is through downregulating the expression of Cancerous Inhibitor of PP2A (CIP2A), the latter, is found upregulated in Alzheimer's disease (AD) brains and participates in the development of AD. In this study, we explored the application

Urinary plasminogen/plasmin, or plasmin (ogen) uria, has been demonstrated in proteinuric patients and exposure of cultured podocytes to plasminogen results in injury via oxidative stress pathways. A causative role for plasmin (ogen) as a “second hit” in kidney disease progression has yet to have been demonstrated in vivo. Additionally, association between plasmin (ogen) uria and kidney function in

Dynamin 1 is a neuronal endocytic protein that participates in vesicle formation by scission of invaginated membranes. Dynamin 1 is also expressed in the kidney; however, its physiological significance to this organ remains unknown. Here, we show that dynamin 1 is crucial for microtubule organization and stabilization in glomerular podocytes. By immunofluorescence and immunoelectron microscopy, dynamin

Estrogen receptor alpha (ERα) is a ligand‐dependent transcription regulator, containing two transactivation functional domains, AF‐1 and AF‐2. The selective estrogen receptor modulators (SERMs), including 4‐hydroxytamoxifen (4OHT), activate AF‐1 preferentially rather than AF‐2. However, it is unclear whether this specific function is related to the tissue‐selective functionality of SERMs. Moreover

Estrogen treatment increases bone mass and reduces fat mass but is associated with adverse effects in postmenopausal women. Knowledge regarding tissue‐specific estrogen signaling is important to aid the development of new tissue‐specific treatments. We hypothesized that the posttranslational modification phosphorylation in estrogen receptor alpha (ERα) may modulate ERα activity in a tissue‐dependent

Hepatitis is an important health problem worldwide. Novel molecular targets are in demand for detection and management of hepatitis. Hepatoma‐derived growth factor (HDGF) has been delineated to participate in hepatic fibrosis and liver carcinogenesis. However, the relationship between hepatitis and HDGF remains unclear. This study aimed to elucidate the role of HDGF during hepatitis using concanavalin

5‐hydroxymethylcytosine (5hmC) is an intermediate stage of DNA de‐methylation. Its location in the genome also serves as an important regulatory signal for many biological processes and its levels change significantly with the etiology of Alzheimer's disease (AD). In keeping with this relationship, the TET family of enzymes which convert 5‐methylcytosine (5mC) to 5hmC are responsive to the presence

Intestinal inflammatory disorders, such as inflammatory bowel disease, are major contributors to mortality and morbidity in humans and animals worldwide. While some native peptides have great potential as therapeutic agents against intestinal inflammation, potential cytotoxicity, anti‐inciting action, and suppression of anti‐inflammatory activity may limit their development as anti‐inflammatory agents

Importin α proteins play a central role in the transport of cargo from the cytoplasm to the nucleus. In this study, we observed that male knock‐out mice for importin α4, which is encoded by the Kpna4 gene (Kpna4−/−), were subfertile and yielded smaller litter sizes than those of wild‐type (WT) males. In contrast, mice lacking the closely related importin α3 (Kpna3−/−) were fertile. In vitro fertilization

Midkine (MDK) might mediate the proangiogenic effect of intermittent hypoxia (IH) in patients with obstructive sleep apnea (OSA) and cutaneous melanoma (CM). We compare circulating MDK in CM patients with and without OSA, and their relationship with tumor aggressiveness, while exploring in vitro effects of soluble MDK on human lymphatic endothelial (HLEC) and melanoma cell proliferation. In 360 CM

Long noncoding RNAs (lncRNAs) have emerged as key regulators in a variety of cellular processes that influence disease states. In particular, many lncRNAs are genetically or epigenetically deregulated in cancer. However, whether lncRNA alterations are passengers acquired during cancer progression or can act as tumorigenic drivers is a topic of ongoing investigation. In this review, we examine the current

Organisms adapt to their environment through coordinated changes in mitochondrial function and metabolism. The mitochondrial protonmotive force (PMF) is an electrochemical gradient that powers ATP synthesis and adjusts metabolism to energetic demands via cellular signaling. It is unknown how or where transient PMF changes are sensed and signaled due to the lack of precise spatiotemporal control in

Poly (rC)‐binding protein 1 (PCBP1), an RNA‐ or DNA‐binding protein with a relative molecular weight of 38 kDa, which is characterized by downregulation in many cancer types. Numerous cases have indicated that PCBP1 could be considered as a tumor suppressor to inhibit tumorigenesis, development, and metastasis. In the current review, we described the multilevel regulatory roles of PCBP1, including

Cell surface trafficking of many G protein‐coupled receptors is tightly regulated. Among them, the mandatory heterodimer GABAB receptor for the main inhibitory neurotransmitter, γ‐aminobutyric acid (GABA), is a model. In mammals, its cell surface trafficking is highly controlled by an endoplasmic reticulum retention signal in the C‐terminal intracellular region of the GB1 subunit that is masked through

HIV‐1 enters the brain by altering properties of the blood‐brain barrier (BBB). Recent evidence indicates that among cells of the BBB, pericytes are prone to HIV‐1 infection. Occludin (ocln) and caveolin‐1 (cav‐1) are critical determinants of BBB integrity that can regulate barrier properties of the BBB in response to HIV‐1 infection. Additionally, Alix is an early acting endosomal factor involved

It is becoming clear that several human pathologies are caused by altered metabolic adaptations. During liver development, there are physiological changes, from the predominant utilization of glucose (fetal life) to the use of lipids (postnatal life). Fasting is another physiological stress that elicits well‐known metabolic adjustments. We have reported the metabolic properties of cardiotrophin‐1 (CT‐1)

Ras‐related C3 botulinum toxin substrate 1 (Rac1) is a member of the Rho family of GTPases that functions as a molecular switch to regulate many important cellular events including actin cytoskeleton remodeling during neurite outgrowth. Engulfment and cell motility 1 (ELMO1)‐dedicator of cytokinesis 1 (DOCK180) is a bipartite guanine nucleotide exchange factor (GEF) complex that has been reported to

Locally produced in human granulosa cells of the developing follicle, bone morphogenetic protein 2 (BMP2) plays a crucial role in the regulation of ovarian folliculogenesis and luteal formation. Brain‐derived neurotrophic factor (BDNF) is an intraovarian neurotrophic factor that has been shown to promote oocyte maturation and subsequent fertilization competency. At present, little is known regarding

Immune dysregulation is among the main adverse outcomes of spaceflight. Despite the crucial role of the antibody repertoire in host protection, the effects of spaceflight on the human antibody repertoire are unknown. Consequently, using high‐throughput sequencing, we examined the IgM repertoire of five cosmonauts 25 days before launch, after 64 ± 11 and 129 ± 20 days spent on the International Space

Inorganic arsenic (iAs/As2O32−) is an environmental toxicant found in watersheds around the world including in densely populated areas. iAs is a class I carcinogen known to target the skin, lungs, bladder, and digestive organs, but its role as a primary breast carcinogen remains controversial. Here, we examined a different possibility: that exposure to iAs promotes the transition of well‐differentiated

Enterotoxigenic Bacteroides fragilis (ETBF) is a commensal bacterium of great importance to human health due to its ability to induce colitis and cause colon tumor formation in mice through the production of B. fragilis toxin (BFT). The formation of tumors is dependent on a pro‐inflammatory signaling cascade, which begins with the disruption of epithelial barrier integrity through cleavage of E‐cadherin

Intrauterine growth restriction (IUGR) leads to offspring obesity. In a maternal food restriction (MFR) during pregnancy‐related IUGR rat model, bone marrow stem cells showed enhanced adipogenic programming; however, the effect of IUGR on white adipose tissue (WAT) progenitors is unknown. Here, by mRNA and functional profiling, we determined sex‐specific adipogenic programming of WAT progenitors isolated

Vasomotor reactions of prostacyclin (prostaglandin I2; PGI2) can be collectively modulated by thromboxane prostanoid receptor (TP), E‐prostanoid receptor‐3 (EP3), and the vasodilator I prostanoid receptor (IP). This study aimed to determine the direct effect of PGI2 on renal arteries and/or the whole renal vasculature and how each of these receptors is involved. Experiments were performed on vessels

It is considered that intestinal barrier dysfunction and systemic endotoxemia drive obesity and its related complications. However, what causes barrier dysfunction remains to be elucidated. Here, we showed that the gut microbiota from high‐fat diet (HFD)‐fed mice had impaired ability to degrade dietary flavonoids, and in correspondence, the microbial‐derived flavonoid metabolite desaminotyrosine (DAT)

Extracellular trafficking of tumor necrosis factor receptor superfamily (TNFRSF) is tightly regulated, disruption of which triggers various autoinflammatory disorders, including TNF receptor‐associated periodic syndrome (TRAPS). Here, we provide thus far unraveled molecular basis of noncysteine mutations in TNFR1 ectodomain where loss of an aromatic moiety in cysteine‐rich domain (CRD) 2 results in

A successful acute inflammatory response results in the elimination of infectious agents by neutrophils and monocytes, followed by resolution and repair through tissue‐resident and recruited macrophages. Resolvins (D‐series and E‐series) are pro‐resolving lipid mediators involved in resolution and tissue repair, whose intracellular signaling remains of interest. Here, we report that D‐series resolvins

Voltage‐gated proton channels (Hv1/VSOP), encoded by Hvcn1, are important regulator of reactive oxygen species (ROS) production in many types of immune cells. While in vitro studies indicate that Hv1/VSOP regulates ROS production by maintaining pH homeostasis, there are few studies investigating the functional importance of Hv1/VSOP in vivo. In the present study, we first show that Hv1/VSOP is functionally

Mammalian Cysteine‐RIch Secretory Protein (CRISP) family includes four members present in sperm and reported to regulate Ca2+ channels and fertilization. Based on our previous observations using single knockouts models and suggesting the existence of functional compensation among CRISP proteins, we investigated their relevance for male fertility by generating multiple Crisp gene mutants by CRISPR/Cas9

Exosomes are extracellular vesicles that mediate the transport of intracellular molecules, including neurodegenerative agents. Exogenously administrated ceramides have been implicated in the acceleration of exosome production by neurons; however, the molecular machinery involved in this process is unknown. Here, we found that ceramides, especially those consisting of long fatty acids, were internalized

The ability of skeletal muscle to regenerate declines significantly with aging. The expression of aryl hydrocarbon receptor nuclear translocator (ARNT), a critical component of the hypoxia signaling pathway, was less abundant in skeletal muscle of old (23‐25 months old) mice. This loss of ARNT was associated with decreased levels of Notch1 intracellular domain (N1ICD) and impaired regenerative response

Although sleep disturbances are common co‐morbidities of metabolic diseases, the underlying processes linking both are not yet fully defined. Changes in the duration of sleep are paralleled by changes in the levels of insulin‐like growth factor‐I (IGF‐I), an anabolic hormone that shows a circadian pattern in the circulation and activity‐dependent entrance in the brain. However, the specific role, if

Pfannkuch, L., Hurwitz, R., Trauisen, J., Sigulla, J., Poeschke, M., Matzner, L., Kosma, P., Schmid, M. and Meyer, T.F. (2019), ADP heptose, a novel pathogen‐associated molecular pattern identified in Helicobacter pylori. Faseb, 33: 9087‐9099. doi:10.1096/fj.201802555R. It has come to the authors’ attention that the H. pylori P12ΔrfaD mutant described in this paper is in fact a double mutant for P12ΔrfaE/ΔrfaD

Base editing technology enables the generation of precisely genome‐modified animal models. In this study, we applied base editing to chicken, an important livestock animal in the fields of agriculture, nutrition, and research through primordial germ cell (PGC)‐mediated germline transmission. Using this approach, we successfully produced two genome‐modified chicken lines harboring mutations in the genes

The nonprofit Federation of American Societies for Experimental Biology (FASEB) sponsors a series of Science Research Conferences (SRCs) each year. These conferences offer scientists a collegial and relaxing environment to discuss and explore new findings and approaches to specific research areas. They feature small‐group settings in which scientists, faculty, postdoctoral fellows, and graduate students

Topical application of extracellular calreticulin (eCRT), an ER chaperone protein, in animal models enhances wound healing and induces tissue regeneration evidenced by epidermal appendage neogenesis and lack of scarring. In addition to chemoattraction of cells critical to the wound healing process, eCRT induces abundant neo‐dermal extracellular matrix (ECM) formation by 3 days post‐wounding. The purpose

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the cause of the global pandemic of coronavirus disease‐2019 (COVID‐19). SARS‐CoV‐2 is a zoonotic disease, but little is known about variations in species susceptibility that could identify potential reservoir species, animal models, and the risk to pets, wildlife, and livestock. Certain species, such as domestic cats and tigers, are susceptible

In the article, “Data driven mathematical modeling reveals the dynamic mechanism of MSC‐induced neovascularization” by Yingting Yu, Qiaojun Situ, Wangyue Jia, Junxiang Li, Qiong Wu, and Jinzhi Lei, in FASEB J. March 2019 33:3496–3509 (doi: 10.1096/fj.201801652R), there is an omission in the Acknowledgments. The correct Acknowledgments are as follows: This research was supported by the Natural Sciences

Decidualization of the endometrial stroma is an essential differentiation process for embryo implantation and maintenance of pregnancy. We previously reported that protein phosphatase 2A (PP2A) acts as a key mediator during cAMP‐induced decidualization of human endometrial stromal cells (hESCs). However, the mechanism underlying its activation has remained obscure in hESCs. In the present study, we

Mammalian LGR5 and LGR4, markers of adult stem cells, are involved in many physiological functions by enhancing WNT signaling. However, whether LGR5 and LGR4 are coupled to other intracellular signaling pathways to regulate stem cell function remains unknown. Here, we show that LGR5 and LGR4 can constitutively activate NF‐κB signaling in a ligand‐independent manner, which is dependent on their C‐termini

The nonprofit Federation of American Societies for Experimental Biology (FASEB) sponsors a series of Science Research Conferences (SRCs) each year. These conferences offer scientists a collegial and relaxing environment to discuss and explore new findings and approaches to specific research areas. The Translational Neuroimmunology Conference: From Mechanisms to Therapeutics was held June 29‐30. This

SCFAs are primarily produced in the colon by bacterial fermentation of nondigestible carbohydrates. Besides providing energy, SCFAs can suppress development of colon cancer. The mechanism, however, remains elusive. Here, we demonstrate that the SCFA propionate upregulates surface expression of the immune stimulatory NKG2D ligands, MICA/B by imposing metabolic changes in dividing cells. Propionate‐mediated

Type I collagen, which is mainly composed of collagen type I alpha 1 chain (COL1A1), is the most abundant extracellular matrix (ECM) protein in the mammalian ovary; and the cyclical remodeling of the ECM plays an essential role in the regulation of corpus luteum formation. Our previous studies have demonstrated that TGF‐β1 is a potent inhibitor of luteinization in human granulosa‐lutein (hGL) cells

Mesangial lesions and podocyte injury are essential manifestations of the progression of diabetic kidney disease (DKD). Although cross‐communication between mesangial cells (MCs) and podocytes has recently been suggested by the results of single‐nucleus RNA sequencing analyses, the molecular mechanisms and role in disease progression remain elusive. Our cDNA microarray data of diabetic mouse glomeruli

Introduction: Cyclic adenosine monophosphate (AMP)‐responsive element‐binding protein H (CREBH), an endoplasmic reticulum‐anchored transcription factor essential for lipid metabolism and inflammation in nonalcoholic fatty liver disease (NAFLD), is covalently modified by N‐acetylglucosamine. Glycosylation is a ubiquitous type of protein involved in posttranslational modifications, and plays a critical

Pericytes promote vessel stability and their dysfunction causes pathologies due to blood vessel leakage. Previously, we reported that Olfactomedin‐like 3 (Olfml3) is a matricellular protein with proangiogenic properties. Here, we explored the role of Olfml3 in a knockout mouse model engineered to suppress this protein. The mutant mice exhibited vascular defects in pericyte coverage, suggesting that

The more than 100 SARS‐CoV‐2 vaccines in development include at least two based on the introduction into subjects of a messenger RNA for one of the virus' proteins, anticipating its translation in an immunogenic protein. In two early studies, the results have been somewhat encouraging, although the potency of the immune responses is not known (at this writing, July 31) nor is the durability of the

Enrichment of neurally derived extracellular vesicles of several cell‐types from plasma for protein quantification longitudinally in living patients with Alzheimer’s disease has permitted the development of a tentative temporal framework of initiating events, progression mechanisms, and amplification processes. Interactions of beta‐amyloid peptides with an elevated level of their normal prion protein

The representation of women and scientists from underrepresented groups (URGs), including Black/African Americans, Hispanic/Latinx, Pacific Islanders, and American Indians, diminishes as individuals advance in their careers from training to senior leadership positions. Correcting this imbalance requires integrated strategies to achieve inclusive excellence within the scientific workforce reflected

Succinate receptor GPR91 is one of G protein‐coupled receptors (GPCRs), and is expressed in a variety of cell types and tissues. Succinate is its natural ligand, and its activation represents that an intrinsic metabolic intermediate exerts a regulatory role on many critical life processes involving pathophysiologic mechanisms, such as innate immunity, inflammation, tissue repair, and oncogenesis. With

Mitochondrial metabolism must constantly adapt to stress conditions in order to maintain bioenergetic levels related to cellular functions. This absence of proper adaptation can be seen in a wide array of conditions, including cancer. Metabolic adaptation calls on mitochondrial function and draws on the mitochondrial reserve to meet increasing needs. Among mitochondrial respiratory parameters, the

Angiogenesis is required for normal development and occurs as a pathological step in a variety of disease settings, such as cancer, ocular diseases, and ischemia. Recent studies have revealed the role of CD44, a widely expressed cell surface adhesion molecule, in promoting pathological angiogenesis and the development of its associated diseases through its regulation of diverse function of endothelial

Lysine acetylation is a posttranslational modification that occurs on thousands of human proteins, most of which are cytoplasmic. Acetylated proteins are involved in numerous cellular processes and human diseases. Therefore, how the acetylation/deacetylation cycle is regulated is an important question. Eleven metal‐dependent lysine deacetylases (KDACs) have been identified in human cells. These enzymes

The presence of DNA in the cytosol is usually a sign of microbial infections, which alerts the host innate immune system to mount a defense response. Cyclic GMP‐AMP synthase (cGAS) is a critical cytosolic DNA sensor that elicits robust innate immune responses through the production of the second messenger, cyclic GMP‐AMP (cGAMP), which binds and activates stimulator of interferon genes (STING). However

Cutaneous pathological scars are fibrotic lesions that grow continuously, invade the adjacent skin, and are erythematous, itchy, and painful. Their etiology remains unclear but may involve genetic, local mechanical, and systemic factors. Here, we will summarize the main systemic factors that shape cutaneous pathological scarring, especially keloid formation and aggravation. They include circulating

COVID‐19 may cause pneumonia, acute respiratory distress syndrome, cardiovascular alterations, and multiple organ failure, which have been ascribed to a cytokine storm, a systemic inflammatory response, and an attack by the immune system. Moreover, an oxidative stress imbalance has been demonstrated to occur in COVID‐19 patients. N‐ Acetyl‐L‐cysteine (NAC) is a precursor of reduced glutathione (GSH)

Ablation of miR‐144/451 disrupts homeostasis of erythropoiesis. Myc, a protooncogenic protein, is essential for erythroblast proliferation but commits rapid downregulation during erythroid maturation. How erythroblasts orchestrate maturation processes through coding and non‐coding genes is largely unknown. In this study, we use miR‐144/451 knockout mice as in vivo model, G1E, MEL erythroblast lines