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| Open AccessHigh-dimensional topographic organization of visual features in the primate temporal lobe
The functional organisation of the inferotemporal cortex is not well understood. Here, the authors construct a multi-dimensional space of visual features using deep neural networks, and show the spatial organisation of feature preference in both human and monkey inferotemporal cortex.
- Mengna Yao
- , Bincheng Wen
- & Le Chang
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Article
| Open AccessIncreasing associative plasticity in temporo-occipital back-projections improves visual perception of emotions
Temporo-occipital areas are involved in perceiving emotional faces. Here, the authors show that strengthening back-projections from temporal to occipital areas enhances visual cortex’s response to face stimuli and perception of emotions from them.
- Sara Borgomaneri
- , Marco Zanon
- & Alessio Avenanti
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Article
| Open AccessSRC and TKS5 mediated podosome formation in fibroblasts promotes extracellular matrix invasion and pulmonary fibrosis
The activation and accumulation of lung fibroblasts resulting in aberrant deposition of extracellular matrix components is a pathogenic hallmark of idiopathic pulmonary fibrosis. Here, the authors show that the formation of podosomes in lung fibroblasts stimulates extracellular matrix invasion in a mouse model of the disease, suggesting that pharmacological targeting of podosome formation or organization might be a therapeutic option.
- Ilianna Barbayianni
- , Paraskevi Kanellopoulou
- & Vassilis Aidinis
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Article
| Open AccessDeficiency of endothelial sirtuin1 in mice stimulates skeletal muscle insulin sensitivity by modifying the secretome
Endothelial Sirtuin1 downregulation in metabolic disorders causes vascular dysfunction and inflammation. Here, the authors show that deficiency of endothelial Sirtuin1, while having deleterious effects on the vasculature, stimulates skeletal muscle insulin sensitivity and improves glucose disposal.
- Qiuxia Li
- , Quanjiang Zhang
- & Kaikobad Irani
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Article
| Open AccessCD44 connects autophagy decline and ageing in the vascular endothelium
Mechanisms underlying the connection between autophagy decline and vascular endothelial cell (VEC) ageing remain unclear. Here, the authors identify a key role for CD44 in controlling autophagy and ageing in VECs, and this function is conserved in nematodes.
- Lu Zhang
- , Peichang Yang
- & Shiwei Ma
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Article
| Open AccessPeroxisomal compartmentalization of amino acid biosynthesis reactions imposes an upper limit on compartment size
Compartmentalization is thought to modulate metabolic flux by spatially segregating enzymes and their coupled reactants. Here, the authors show that peroxisomal compartmentalization of amino acid synthesis imposes an upper limit on compartment size.
- Ying Gu
- , Sara Alam
- & Snezhana Oliferenko
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Article
| Open AccessCold-activated brown fat-derived extracellular vesicle-miR-378a-3p stimulates hepatic gluconeogenesis in male mice
During cold exposure, activated brown adipose tissue takes up a large amount of circulating glucose to fuel thermogenesis. Here, the authors show that cold stress enhances the packaging of miR-378a-3p into BAT-derived EVs, which are delivered to the liver and consequently stimulates gluconeogenesis.
- Jinhong Xu
- , Le Cui
- & Xiaohong Jiang
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Article
| Open AccessMKP1 promotes nonalcoholic steatohepatitis by suppressing AMPK activity through LKB1 nuclear retention
Nonalcoholic steatohepatitis (NASH) is a devastating type of liver disease that is caused by hepatocellular death which triggers liver inflammation and fibrosis. Here, the authors show that MAP kinase phosphatase-1 promotes hepatocellular death thus, driving the development of NASH.
- Bin Qiu
- , Ahmed Lawan
- & Anton M. Bennett
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Article
| Open AccessControl of intracellular pH and bicarbonate by CO2 diffusion into human sperm
Bicarbonate (HCO3−) is critical in sperm for stimulation of cAMP synthesis during fertilization, though there is dispute over how HCO3− is transported into sperm. Here the authors use limit-of-detection LC/MS to characterize sperm protein expression and show that HCO3− is produced from CO2 diffusion into sperm rather than active transport.
- Elena Grahn
- , Svenja V. Kaufmann
- & U.Benjamin Kaupp
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Article
| Open AccessThe interplay between dietary fatty acids and gut microbiota influences host metabolism and hepatic steatosis
Here, Schoeler et al. investigate how interaction between dietary lipids and the gut microbiota affect hepatic steatosis and host metabolism, showing that dietary lipids impact the gut microbiota composition independent on fiber intake in humans and mice.
- Marc Schoeler
- , Sandrine Ellero-Simatos
- & Robert Caesar
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Article
| Open AccessPurinergic signaling mediates neuroglial interactions to modulate sighs
Sighs are augmented breaths necessary to maintain normal breathing. Here, the authors show that sighs are generated within the preBötzinger complex by emergent network properties that involve neuroglial interactions mediated by purinergic signaling as well as intrinsic and extrinsic modulatory inputs.
- Liza J. Severs
- , Nicholas E. Bush
- & Jan-Marino Ramirez
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Article
| Open AccessHepatic SREBP signaling requires SPRING to govern systemic lipid metabolism in mice and humans
Hendrix et al show that absence of hepatic Spring dramatically lowers levels of lipids in the liver and plasma in mice, and protects from development of diet-induced steatosis. In line, genetic variation in SPRING is associated with lipid levels in humans.
- Sebastian Hendrix
- , Jenina Kingma
- & Noam Zelcer
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Article
| Open AccessImpaired Plakophilin-2 in obesity breaks cell cycle dynamics to breed adipocyte senescence
Plakophilin-2 is a key component of desmosomes required to maintain cardiac tissue cohesion. Here the authors uncover a previously unknown defect in cell cycle and adipocyte senescence due to impaired Plakophilin-2 in subjects with obesity.
- Aina Lluch
- , Jessica Latorre
- & Francisco J. Ortega
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Article
| Open AccessSYPL1 defines a vesicular pathway essential for sperm cytoplasmic droplet formation and male fertility
The cytoplasmic droplet is an elusive structure of mammalian sperm. Here, the authors uncover a key gene that defines a vesicular pathway essential for cytoplasmic droplet formation and male fertility.
- Jiali Liu
- , Louis Hermo
- & Chen Chen
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Article
| Open AccessBat teeth illuminate the diversification of mammalian tooth classes
Despite their key role in the evolution of mammals, the origin and diversification of tooth classes (incisors, canines, premolars and molars) remain relatively obscure. Here the authors use integrative approaches to explain the independent evolution and rapid diversification of two tooth classes, premolar and molars, in noctilionoid bats.
- Alexa Sadier
- , Neal Anthwal
- & Karen E. Sears
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Article
| Open AccessEndothelial ERα promotes glucose tolerance by enhancing endothelial insulin transport to skeletal muscle
Estrogen has anti-diabetic effects via estrogen receptor alpha (ERα). Here, authors show that via coupled nuclear and non-nuclear actions, ERα in endothelial cells promotes insulin transport to skeletal muscle to foster normal glucose homeostasis.
- Anastasia Sacharidou
- , Ken Chambliss
- & Philip W. Shaul
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Matters Arising
| Open AccessReply to: Fluid signal suppression characteristics of 3D-FLAIR with a T2 selective inversion pulse in the skull base
- Mehmet Sait Albayram
- , Garrett Smith
- & Onder Albayram
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Article
| Open AccessREPTOR and CREBRF encode key regulators of muscle energy metabolism
Obesity and cancer-induced cachexia are linked to an impairment in the ability of muscle to use glucose or lipids interchangeably as energy substrates. Here, the authors propose that Drosophila REPTOR and its mammalian ortholog CREBRF act as key transcriptional regulators of fuel choice in muscle.
- Pedro Saavedra
- , Phillip A. Dumesic
- & Norbert Perrimon
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Article
| Open AccessMTH1 protects platelet mitochondria from oxidative damage and regulates platelet function and thrombosis
MTH1 hydrolyzes oxidized nucleotides to prevent their mis-incorporation into DNA under oxidative stress. Here, the authors show that MTH1 is expressed in platelets and its deficiency increases mitochondrial DNA oxidative damage, impairs platelet function and hemostasis.
- Yangyang Ding
- , Xiang Gui
- & Jianlin Qiao
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Article
| Open AccessStructural basis of agonist specificity of α1A-adrenergic receptor
α1-adrenergic receptors (α1- AR) play critical roles in the cardiovascular and nervous systems. Here, the authors report molecular insights into the mechanisms underlying the discrimination between α1A-AR and α1B-AR by the agonist A61603.
- Minfei Su
- , Jinan Wang
- & Xin-Yun Huang
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Article
| Open AccessBone marrow adiposity modulation after long duration spaceflight in astronauts
Bone marrow adiposity is linked to disease, and it is unknown how it is modulated during space travel. Here, the authors show that astronauts returning from ISS missions had decreased marrow fat and increased hematopoiesis and bone formation, suggesting that adipose reserves in the bone marrow might be used as an energy source to counteract anemia and bone loss associated with space flight.
- Tammy Liu
- , Gerd Melkus
- & Guy Trudel
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Article
| Open AccessStimulus edges induce orientation tuning in superior colliculus
Whether orientation columns exist in the mouse superior colliculus remains unknown. Here, the authors found that orientation columns are dynamically induced by stimulus edge and the resulting stimulus-dependent tuning is associated with saliency encoding.
- Yajie Liang
- , Rongwen Lu
- & Na Ji
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Article
| Open AccessModulatory dynamics of periodic and aperiodic activity in respiration-brain coupling
Respiration modulates neural oscillations, but its link to aperiodic brain activity is not known. With a multi-centre human MEG and EEG study, here the authors show that fluctuations of aperiodic brain activity are phase-locked to the respiratory cycle.
- Daniel S. Kluger
- , Carina Forster
- & Joachim Gross
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Article
| Open AccessNon-invasive electromechanical assessment during atrial fibrillation identifies underlying atrial myopathy alterations with early prognostic value
Electromechanical characterization during atrial fibrillation (AF) remains a significant gap in the understanding of AF-related atrial myopathy. Here, the authors use non-invasive atrial electromechanical assessment during AF to identify early remodeling changes associated with underlying myopathy, which in the clinic decrease the probability of acute and mid-term successful rhythm control.
- Daniel Enríquez-Vázquez
- , Jorge G. Quintanilla
- & David Filgueiras-Rama
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Article
| Open AccessMyonectin protects against skeletal muscle dysfunction in male mice through activation of AMPK/PGC1α pathway
Here the authors show that myonectin functions as a protective factor against age-associated, disuse-induced or steroid-induced muscle atrophy, suggesting that myonectin represents a therapeutic target for preventing skeletal muscle dysfunction.
- Yuta Ozaki
- , Koji Ohashi
- & Noriyuki Ouchi
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Article
| Open AccessTRIM28 modulates nuclear receptor signaling to regulate uterine function
This paper identifies Tripartite motif-containing 28 (TRIM28) as a novel modulator of steroid hormone signaling. TRIM28 deficiency disrupts uterine cell functions and composition leading to fertility defects
- Rong Li
- , Tianyuan Wang
- & Francesco J. DeMayo
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Article
| Open AccessMultiparametric senescent cell phenotyping reveals targets of senolytic therapy in the aged murine skeleton
Technical challenges have previously hindered the detailed study of in vivo senescent cells. Here, the authors deeply characterize senescent skeletal cells across murine aging, establishing CD24 as a marker of osteolineage cells cleared by senolytics.
- Madison L. Doolittle
- , Dominik Saul
- & Sundeep Khosla
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Article
| Open AccessLysophosphatidylserine induces necrosis in pressure overloaded male mouse hearts via G protein coupled receptor 34
iPLA2β produces lipid mediators and induces nuclear shrinkage in caspase-independent cell death. Here, the authors show that lysophosphatidylserine generated by iPLA2β induces necrotic cardiomyocyte death mediated through GPR34 in pressure-overloaded mouse hearts, leading to cardiac dysfunction.
- Ryuta Sugihara
- , Manabu Taneike
- & Kinya Otsu
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Article
| Open AccessHippocampal ensemble dynamics and memory performance are modulated by respiration during encoding
Breathing might be crucial for cognition during both offline and online brain states. Here, the authors show that temporal apnea induced by activating the PreBötzinger complex during memory formation resulted in memory impairments.
- Nozomu H. Nakamura
- , Hidemasa Furue
- & Yoshitaka Oku
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Article
| Open AccessIntermediate filaments associate with aggresome-like structures in proteostressed C. elegans neurons and influence large vesicle extrusions as exophers
High neuronal proteostress can trigger the production of aggregate-filled exophers in C. elegans. Here authors show that such extrusion relies on aggregate-associated intermediate filaments and adaptors.
- Meghan Lee Arnold
- , Jason Cooper
- & Monica Driscoll
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Article
| Open AccessDetermining the metabolic effects of dietary fat, sugars and fat-sugar interaction using nutritional geometry in a dietary challenge study with male mice
The role of dietary fat vs sugar in the global obesity epidemic remains controversial. Using Nutritional Geometry methodology, the authors show that, in mice, both fats and sugars could lead to adverse metabolic outcomes, depending on the dietary context.
- Jibran A. Wali
- , Duan Ni
- & Stephen J. Simpson
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Article
| Open AccessInvolvement of skin TRPV3 in temperature detection regulated by TMEM79 in mice
The TRPV3 ion channel has been reported to contribute to thermosensation. Here, the authors use electrophysiology and a thermal gradient ring method to show a transmembrane protein TMEM79 negatively regulates TRPV3-mediate currents and changed thermal preference.
- Jing Lei
- , Reiko U. Yoshimoto
- & Makoto Tominaga
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Article
| Open AccessChemogenetic dissection of a prefrontal-hypothalamic circuit for socially subjective reward valuation in macaques
How subjective reward value is affected by social comparison remains poorly understood. Here, the authors show a crucial role for the circuit from the medial prefrontal cortex to the lateral hypothalamus in subjective value modulation in social contexts.
- Atsushi Noritake
- , Taihei Ninomiya
- & Masaki Isoda
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Article
| Open AccessThe muscle-enriched myokine Musclin impairs beige fat thermogenesis and systemic energy homeostasis via Tfr1/PKA signaling in male mice
Interorgan communications play key roles in the regulation of whole-body energy metabolism. Here, the authors report the myokine Musclin as a negative regulator of beige adipose thermogenesis and systemic energy homeostasis through Tfr1/PKA signalling mediated muscle fat crosstalk.
- Lu Jin
- , Shuang Han
- & Zhuo-Xian Meng
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Article
| Open AccessA spatially anchored transcriptomic atlas of the human kidney papilla identifies significant immune injury in patients with stone disease
Kidney stone disease causes significant morbidity and increases in health care utilization. Here, the authors define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human renal papilla and identify associated urinary biomarkers.
- Victor Hugo Canela
- , William S. Bowen
- & Tarek M. El-Achkar
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Article
| Open AccessRestoration of PITPNA in Type 2 diabetic human islets reverses pancreatic beta-cell dysfunction
Type 2 diabetes (T2D) is characterized by pancreatic beta-cell failure. Here, the authors show restoration of Phosphatidylinositol transfer protein alpha (PITPNA), a mediator of PtdIns-4-phosphate synthesis in the trans-Golgi network, in human T2D islets reverses impaired insulin granule maturation, exocytosis, and ER stress.
- Yu-Te Yeh
- , Chandan Sona
- & Matthew N. Poy
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Article
| Open AccessA renal YY1-KIM1-DR5 axis regulates the progression of acute kidney injury
KIM1 is dramatically upregulated in acute kidney injury (AKI) and but how KIM1 affects AKI remains unknown. Here, the authors report that renal specific Kim1 knockout relieves AKI, unveil a YY1-KIM1-DR5 axis in the progression of AKI, and suggest potential therapeutic strategies against AKI.
- Chen Yang
- , Huidie Xu
- & Ling Zheng
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Article
| Open AccessSynaptotagmin-1-dependent phasic axonal dopamine release is dispensable for basic motor behaviors in mice
Synaptotagmin 1 is involved in dopamine release. Here the authors investigate the effect of loss of Syt1 in midbrain dopaminergic neurons in mice, and find that unconditioned motor behaviour and motivation for food, are intact.
- Benoît Delignat-Lavaud
- , Jana Kano
- & Louis-Éric Trudeau
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Article
| Open AccessThe structural pathology for hypophosphatasia caused by malfunctional tissue non-specific alkaline phosphatase
Hypophosphatasia (HPP) is a bone disease caused by mutations in tissue non-specific alkaline phosphatase (TNAP). Here, authors solved the crystal and cryoEM structures of TNAP, shedding light on the molecular mechanisms underlying HPP.
- Yating Yu
- , Kewei Rong
- & An Qin
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Article
| Open AccessHighly efficient platelet generation in lung vasculature reproduced by microfluidics
Highly efficient generation of platelets in the vasculature. Here, Zhao et al. show that the mouse platelet precursor cell, megakaryocytes, generate physiological numbers of functional platelets when passaged repeatedly through pulmonary vasculature.
- Xiaojuan Zhao
- , Dominic Alibhai
- & Alastair W. Poole
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Article
| Open AccessLinker histone variant H1.2 is a brake on white adipose tissue browning
Thermogenic adipocytes are ideal targets to counteract obesity and associated metabolic disorders. Here, the authors show a regulatory role of linker histone variant H1.2 on iWAT browning and thermogenesis through an H1.2-IL10rα axis.
- Yangmian Yuan
- , Yu Fan
- & Ling Zheng
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Matters Arising
| Open AccessPotential contribution of PEP carboxykinase-dependent malate dismutation to the hypoxia response in C. elegans
- Rosina Comas-Ghierra
- , Laura Romanelli-Cedrez
- & Gustavo Salinas
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Article
| Open AccessChronic UCN2 treatment desensitizes CRHR2 and improves insulin sensitivity
UCN2 acts as a ligand for the GPCR CRHR2 and there have been conflicting reports on whether UCN2 treatment improves or worsens glucose tolerance. Here, the authors show that acute UCN2 recruits Gs and decreases glucose uptake, while chronic treatment desensitizes CRHR2 and improves glucose uptake.
- Stephen E. Flaherty III
- , Olivier Bezy
- & Zhidan Wu
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Matters Arising
| Open AccessReply to: Potential contribution of PEP carboxykinase-dependent malate dismutation to the hypoxia response in C. elegans
- Mehul Vora
- , Stephanie M. Pyonteck
- & Christopher Rongo
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Article
| Open AccessModeling and therapeutic targeting of inflammation-induced hepatic insulin resistance using human iPSC-derived hepatocytes and macrophages
Hepatic insulin resistance is an established driver of type 2 diabetes but is difficult to model in vitro. Here researchers use co-culture of hepatocytes and macrophages derived from the same human iPSC line to show how inflammation disrupts insulin-mediated regulation of hepatic glucose metabolism and identify targets for therapy of hepatic insulin resistance.
- Marko Groeger
- , Koji Matsuo
- & Holger Willenbring
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Article
| Open AccessTRPA1 activation in non-sensory supporting cells contributes to regulation of cochlear sensitivity after acoustic trauma
The function of TRPA1 channels in the mammalian cochlea is poorly understood. Here, the authors show that TRPA1 channels in supporting cells of the organ of Corti mediate contractile responses that may contribute to temporary shifts in hearing thresholds after noise exposure in mice.
- A. Catalina Vélez-Ortega
- , Ruben Stepanyan
- & Gregory I. Frolenkov
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Article
| Open AccessAcute stress induces long-term metabolic, functional, and structural remodeling of the heart
Takotsubo disease, a stress induced cardiomyopathy mimicking acute coronary syndrome, increases the risk of heart failure and cardiac death. The authors show here that heart function and structure keep on deteriorating continuously after a single acute stress, this snowball effect being triggered by abnormalities incardiac metabolism.
- Thulaciga Yoganathan
- , Mailyn Perez-Liva
- & Bertrand Tavitian
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Article
| Open AccessMitochondrial matrix protein LETMD1 maintains thermogenic capacity of brown adipose tissue in male mice
Brown adipose tissue (BAT) has abundant mitochondria with the unique capability of generating heat via uncoupled respiration. Here, Park et al. identify LETMD1 as a mitochondrial matrix protein enriched in brown adipose tissue (BAT) and reveal a crucial role for it in maintaining brown adipocyte mitochondrial OXPHOS and thermogenesis upon cold stimulus.
- Anna Park
- , Kwang-eun Kim
- & Jae Myoung Suh
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Article
| Open AccessThe role of mechano-regulated YAP/TAZ in erectile dysfunction
Phosphodiesterase type 5 inhibitors (PDE5is) are used to treat erectile dysfunction, however, not all patients respond to PDE5i treatment. Here the authors report that YAP/TAZ activity contributes to erectile dysfunction and targeting YAP/TAZ improves erectile function in a PDE5i non-respondent rat model.
- Mintao Ji
- , Dongsheng Chen
- & Lei Chang