Identification of pathogenic TRAIL-expressing innate immune cells during HIV-1 infection in humanized mice by scRNA-Seq.
AuthorsCheng L,Yu H,Wrobel JA,Li G,Liu P,Hu Z,Xu XN,Su L
JournalJCI insight
PubMed ID32406872
Depletion of CD4(+) T cells during HIV-1 infection is mostly mediated by inflammatory cells via indirect but not clearly defined mechanisms. In this report, we used single-cell RNA-Seq (scRNA-Seq) technology to study HIV-induced transcriptomic change in innate immune cells in lymphoid organs. We performed scRNA-Seq on hCD45(+)hCD3(â)hCD19(â) human leukocytes isolated ... More
Development of a peptide drug restoring AMPK and adipose tissue functionality in cancer cachexia.
JournalMolecular therapy : the journal of the American Society of Gene Therapy
PubMed ID37408309
Cancer cachexia is a severe systemic wasting disease that negatively affects quality of life and survival in patients with cancer. To date, treating cancer cachexia is still a major unmet clinical need. We recently discovered the destabilization of the AMP-activated protein kinase (AMPK) complex in adipose tissue as a key ... More
Long noncoding RNA ENST00000455974 plays an oncogenic role through up-regulating JAG2 in human DNA mismatch repair-proficient colon cancer.
Dosage of key regulators impinge on developmental disorders such as FOXG1 syndrome. Since neither knock-out nor knock-down strategy assures flexible and precise protein abundance control, to study hypomorphic or haploinsufficiency expression remains challenging. We develop a system in human pluripotent stem cells (hPSCs) using CRISPR/Cas9 and SMASh technology, with which ... More
Scrutiny of NolA and NodD1 Regulatory Roles in Symbiotic Compatibility Unveils New Insights into Bradyrhizobium guangxiense CCBAU53363 Interacting with Peanut (Arachis hypogaea) and Mung Bean (Vigna radiata).
Bradyrhizobium guangxiense CCBAU53363 efficiently nodulates peanut but exhibits incompatible interaction with mung bean. By comparing the common nod region with those of other peanut bradyrhizobia efficiently nodulating these two hosts, distinctive characteristics with a single nodD isoform (nodD1) and a truncated nolA were identified. However, the regulatory roles of NodD1 ... More
Overexpressing CrePAPS Polyadenylate Activity Enhances Protein Translation and Accumulation in Chlamydomonas reinhardtii.
The alga Chlamydomonas reinhardtii is a potential platform for recombinant protein expression in the future due to various advantages. Dozens of C. reinhardtii strains producing genetically engineered recombinant therapeutic protein have been reported. However, owing to extremely low protein expression efficiency, none have been applied for industrial purposes. Improving protein ... More
Induction of M2 Macrophages Prevents Bone Loss in Murine Periodontitis Models.
Periodontitis is characterized by the progressive destruction of tooth-supporting alveolar bone, which is mainly caused by chronic inflammation in response to persistent bacterial insult. It has recently become clear that the pathogenesis of periodontitis is associated with a high ratio of proinflammatory M1 (classically activated) macrophages to anti-inflammatory M2 (alternatively ... More
TMEM16E regulates endothelial cell procoagulant activity and thrombosis.
Endothelial cells (ECs) normally form an anticoagulant surface under physiological conditions, but switch to support coagulation following pathogenic stimuli. This switch promotes thrombotic cardiovascular disease. To generate thrombin at physiologic rates, coagulation proteins assemble on a membrane containing anionic phospholipid, most notably phosphatidylserine (PS). PS can be rapidly externalized to ... More
Critical Evaluation of CrAssphage as a Molecular Marker for Human-Derived Wastewater Contamination in the Aquatic Environment.
The discharge of human-derived wastewater represents a major threat to water quality with the potential for waterborne disease outbreaks mainly associated with enteric viruses. To prevent illnesses, indicators associated with fecal contamination are monitored in polluted areas, however, their prevalence often does not correlate well with viral pathogens. In this ... More
Functional Inhibition of Host Histone Deacetylases (HDACs) Enhances in vitro and in vivo Anti-mycobacterial Activity in Human Macrophages and in Zebrafish.
The rapid and persistent increase of drug-resistant Mycobacterium tuberculosis (Mtb) infections poses increasing global problems in combatting tuberculosis (TB), prompting for the development of alternative strategies including host-directed therapy (HDT). Since Mtb is an intracellular pathogen with a remarkable ability to manipulate host intracellular signaling pathways to escape from host ... More
Genome-wide identification and expression profile analysis of the NAC transcription factor family during abiotic and biotic stress in woodland strawberry.
AuthorsZhang H,Kang H,Su C,Qi Y,Liu X,Pu J
JournalPloS one
PubMed ID29897926
The NAC transcription factors involved plant development and response to various stress stimuli. However, little information is available concerning the NAC family in the woodland strawberry. Herein, 37 NAC genes were identified from the woodland strawberry genome and were classified into 13 groups based on phylogenetic analysis. And further analyses ... More
OsPHT1;3 Mediates Uptake, Translocation, and Remobilization of Phosphate under Extremely Low Phosphate Regimes.
Plant roots rely on inorganic orthophosphate (Pi) transporters to acquire soluble Pi from soil solutions that exists at micromolar levels in natural ecosystems. Here, we functionally characterized a rice (Oryza sativa) Pi transporter, Os Phosphate Transporter-1;3 (OsPHT1;3), that mediates Pi uptake, translocation, and remobilization. OsPHT1;3 was directly regulated by Os ... More
Comprehensive analysis of the Gossypium hirsutum L. respiratory burst oxidase homolog (Ghrboh) gene family.
AuthorsWang W,Chen D,Liu D,Cheng Y,Zhang X,Song L,Hu M,Dong J,Shen F
JournalBMC genomics
PubMed ID31996127
BACKGROUND: Plant NADPH oxidase (NOX), also known as respiratory burst oxidase homolog (rboh), encoded by the rboh gene, is a key enzyme in the reactive oxygen species (ROS) metabolic network. It catalyzes the formation of the superoxide anion (O(2)(â¢â)), a type of ROS. In recent years, various studies had shown ... More
Mechanism of Pydiflumetofen Resistance in Fusarium graminearum in China.
Fusarium head blight (FHB), which is primarily caused by Fusarium graminearum, is a widespread and devastating disease of wheat. In the absence of resistant varieties, the control of FHB relies heavily on the application of fungicides, and the new generation SDHI fungicide, pydiflumetofen, has recently been registered in China for ... More
Variable Light Condition Improves Root Distribution Shallowness and P Uptake of Soybean in Maize/Soybean Relay Strip Intercropping System.
In this study, soybean root distribution in an inter-cropping system was influenced by various environmental and biotic cues. However, it is still unknown how root development and distribution in inter-cropping responds to aboveground light conditions. Herein, soybeans were inter- and monocropped with P (phosphorus) treatments of 0 and 20 kg ... More
Gravity Reduced Nitrogen Uptake via the Regulation of Brace Unilateral Root Growth in Maize Intercropping.
Water, nutrient, light, and interspecific facilitation regulation of soil physicochemical properties and root morphology modulate nitrogen (N) uptake in cereal and legume intercropping systems. However, maize root morphological plasticity and N uptake capability response to gravity in the intercropping system remains to be determined. In this study, maize was grown ... More
Conjugated Linoleic Acid Supplementation Improves Maternal High Fat Diet-Induced Programming of Metabolic Dysfunction in Adult Male Rat Offspring.
AuthorsSegovia SA,Vickers MH,Gray C,Zhang XD,Reynolds CM
JournalScientific reports
PubMed ID28751679
The developmental origins of health and disease hypothesis proposes that an adverse early life environment, including in utero exposure to a maternal obesogenic environment, can lead to an increased long-term risk of obesity and related metabolic complications in offspring. We assessed whether maternal supplementation with conjugated linoleic acid (CLA) could ... More
Adipose expression of CREB3L3 modulates body weight during obesity.
We found the hepatic transcription factor Cyclic-AMP Responsive Element Binding Protein 3-like-3 (CREB3L3) to be expressed in adipose tissue, and selectively downregulated in the more metabolically protective subcutaneous adipose tissue in obese mice and humans. We sought to elucidate the specific role of this factor in adipose biology. CREB3L3 fat-specific ... More
NR4A Nuclear Receptors Target Poly-ADP-Ribosylated DNA-PKcs Protein to Promote DNA Repair.
Although poly-ADP-ribosylation (PARylation) of DNA repair factors had been well documented, its role in the repair of DNA double-strand breaks (DSBs) is poorly understood. NR4A nuclear orphan receptors were previously linked to DSB repair; however, their function in the process remains elusive. Classically, NR4As function as transcription factors using a ... More
Expression of Circ_Satb1 Is Decreased in Mesial Temporal Lobe Epilepsy and Regulates Dendritic Spine Morphology.
Mesial temporal lobe epilepsy (mTLE) is a chronic disease characterized by recurrent seizures that originate in the temporal lobes of the brain. Anti-epileptic drugs (AEDs) are the standard treatment for managing seizures in mTLE patients, but are frequently ineffective. Resective surgery is an option for some patients, but does not ... More
ZBED6 regulates Igf2 expression partially through its regulation of miR483 expression.
AuthorsNaboulsi R,Larsson M,Andersson L,Younis S
JournalScientific reports
PubMed ID34593874
The expression of Igf2 in mammals shows a complex regulation involving multiple promoters and epigenetic mechanisms. We previously identified a novel regulatory mechanism based on the interaction between the transcriptional factor ZBED6 and Igf2 intron. Disruption of the ZBED6-Igf2 interaction leads to a dramatic up-regulation of IGF2 expression postnatally. In ... More
The OsGSK2 Kinase Integrates Brassinosteroid and Jasmonic Acid Signaling by Interacting with OsJAZ4.
The crosstalk between brassinosteroid (BR) and jasmonic acid (JA) signaling is crucial for plant growth and defense responses. However, the detailed interplay between BRs and JA remains obscure. Here, we found that the rice (Oryza sativa) Glycogen synthase kinase3 (GSK3)âlike kinase OsGSK2, a conserved kinase serving as a key suppressor ... More
Cytomegalovirus Late Protein pUL31 Alters Pre-rRNA Expression and Nuclear Organization during Infection.
AuthorsWestdorp KN,Sand A,Moorman NJ,Terhune SS
JournalJournal of virology
PubMed ID28659485
The replication cycle of human cytomegalovirus (CMV) leads to drastic reorganization of domains in the host cell nucleus. However, the mechanisms involved and how these domains contribute to infection are not well understood. Our recent studies defining the CMV-induced nuclear proteome identified several viral proteins of unknown functions, including a ... More
Effect of miR-301a/PTEN pathway on the proliferation and apoptosis of cervical cancer.
AuthorsPeng LN,Shi WT,Feng HR,Wei CY,Yin QN
JournalInnate immunity
PubMed ID30943822
The aim of this study was to evaluate the effect of the miR-301a/PTEN pathway in cervical cancer. miR-301a and PTEN expression were measured by quantitative real-time PCR (qRT-PCR) in tissues samples and HeLa cells. PTEN protein level was determined by Western blotting. Dual reporter luciferase assay was performed to validate ... More
Neonatal Osteomacs and Bone Marrow Macrophages Differ in Phenotypic Marker Expression and Function.
JournalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
PubMed ID33900648
Osteomacs (OM) are specialized bone-resident macrophages that are a component of the hematopoietic niche and support bone formation. Also located in the niche, are a second subset of macrophages, namely bone marrow-derived macrophages (BM MÏ). We previously reported that a subpopulation of OM co-express both CD166 and CSF1R (the receptor ... More
Long non-coding RNA XIST promotes osteoporosis by inhibiting the differentiation of bone marrow mesenchymal stem cell by sponging miR-29b-3p that suppresses nicotinamide N-methyltransferase.
AuthorsYu J,Xiao M,Ren G
JournalBioengineered
PubMed ID34486487
Bone formation is important in the development of osteoporosis (OP). Xâinactive specific transcript (XIST), a lncRNA, is involved in this process; however, mode of its action is not known. We compared the serum levels of XIST and miR-29b-3p among the patients with and without OP. In rat bone marrow mesenchymal ... More
Spermidine Is an Intercellular Signal Modulating T3SS Expression in Pseudomonas aeruginosa.
Pseudomonas aeruginosa is a vital opportunistic human bacterial pathogen that causes acute and chronic infections. In this study, we set to determine whether the endogenous spermidine biosynthesis plays a role in regulation of type III secretion system (T3SS). The results showed that deletion of speA and speC, which encode putrescine ... More
Bempedoic acid, an ATP citrate lyase inhibitor, reduces intimal hyperplasia via activation of AMPKα signaling pathway.
AuthorsLiu W,Liu M,Xiong H,Xia L,Yang Q,Chen M,Cai Y,Li S
JournalInternational immunopharmacology
PubMed ID36461594
HIF-α Activation Impacts Macrophage Function during Murine Leishmania major Infection.
Leishmanial skin lesions are characterized by inflammatory hypoxia alongside the activation of hypoxia-inducible factors, HIF-1α and HIF-2α, and subsequent expression of the HIF-α target VEGF-A during Leishmania major infection. However, the factors responsible for HIF-α activation are not known. We hypothesize that hypoxia and proinflammatory stimuli contribute to HIF-α activation ... More
Novel prognostic model established for patients with head and neck squamous cell carcinoma based on pyroptosis-related genes.
We aimed at establishing a risk â score model using pyroptosis-related genes to predict the prognosis of patients with head and neck squamous cell carcinoma (HNSCC). A total of 33 pyroptosis-related genes were selected. We then evaluated the data of 502 HNSCC patients and 44 normal patients from TCGA database. ... More
Naïve-like pluripotency to pave the way for saving the northern white rhinoceros from extinction.
The northern white rhinoceros (NWR) is probably the earthâs most endangered mammal. To rescue the functionally extinct species, we aim to employ induced pluripotent stem cells (iPSCs) to generate gametes and subsequently embryos in vitro. To elucidate the regulation of pluripotency and differentiation of NWR PSCs, we generated iPSCs from ... More
Identification of Leukocyte telomere length-related genetic variants contributing to predisposition of Esophageal Squamous Cell Carcinoma.
AuthorsLi Z,Song Y,Xu Y,Shen Y,Zhang N,Yang M,Yu D
JournalJournal of Cancer
PubMed ID32742450
Background: Cancers may arise from cells with dysregulated telomeric functions due to shorten telomere length. We and others previously found that short leukocyte telomere length was associated with markedly evaluated risk of esophageal squamous cell carcinoma (ESCC). Hence, we hypothesized that single nucleotide polymorphisms (SNPs) associated with shorter telomere length ... More
Mitochondrial biogenesis is transcriptionally repressed in lysosomal lipid storage diseases.
AuthorsYambire KF,Fernandez-Mosquera L,Steinfeld R,Mühle C,Ikonen E,Milosevic I,Raimundo N
JournaleLife
PubMed ID30775969
Perturbations in mitochondrial function and homeostasis are pervasive in lysosomal storage diseases, but the underlying mechanisms remain unknown. Here, we report a transcriptional program that represses mitochondrial biogenesis and function in lysosomal storage diseases Niemann-Pick type C (NPC) and acid sphingomyelinase deficiency (ASM), in patient cells and mouse tissues. This ... More
FtsH2-Dependent Proteolysis of EXECUTER1 Is Essential in Mediating Singlet Oxygen-Triggered Retrograde Signaling in Arabidopsis thaliana.
AuthorsDogra V,Duan J,Lee KP,Lv S,Liu R,Kim C
JournalFrontiers in plant science
PubMed ID28706530
Photosystem II reaction center (PSII RC) and light-harvesting complex inevitably generate highly reactive singlet oxygen ((1)O(2)) that can impose photo-oxidative damage, especially when the rate of generation exceeds the rate of detoxification. Besides being toxic, (1)O(2) has also been ascribed to trigger retrograde signaling, which leads to nuclear gene expression ... More
A LGR5 reporter pig model closely resembles human intestine for improved study of stem cells in disease.
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
PubMed ID37159340
Intestinal epithelial stem cells (ISCs) are responsible for intestinal epithelial barrier renewal; thereby, ISCs play a critical role in intestinal pathophysiology research. While transgenic ISC reporter mice are available, advanced translational studies lack a large animal model. This study validates ISC isolation in a new porcine Leucine Rich Repeat Containing ... More
m(6)A-Mediated PPARA Translational Suppression Contributes to Corticosterone-Induced Visceral Fat Deposition in Chickens.
AuthorsZhou Z,Zhang A,Liu X,Yang Y,Zhao R,Jia Y
JournalInternational journal of molecular sciences
PubMed ID36555401
Excess fat deposition in broilers leads to great economic losses and is harmful to consumersâ health. Chronic stress in the life cycle of chickens could be an important trigger. However, the underlying mechanisms are still unclear. In this study, 30-day-old chickens were subcutaneously injected with 2 mg/kg corticosterone (CORT) twice ... More
Nej1 interacts with Sae2 at DNA double-stranded breaks to inhibit DNA resection.
AuthorsMojumdar A,Adam N,Cobb JA
JournalThe Journal of biological chemistry
PubMed ID35429499
The two major pathways of DNA double-strand break repair, nonhomologous end-joining and homologous recombination, are highly conserved from yeast to mammals. The regulation of 5â²-DNA resection controls repair pathway choice and influences repair outcomes. Nej1 was first identified as a canonical NHEJ factor involved in stimulating the ligation of broken ... More
Translation of human Δ133p53 mRNA and its targeting by antisense oligonucleotides complementary to the 5'-terminal region of this mRNA.
The p53 protein is expressed as at least twelve protein isoforms. Within intron 4 of the human TP53 gene, a P2 transcription initiation site is located and this transcript encodes two p53 isoforms: Î133p53 and Î160p53. Here, the secondary structure of the 5â²-terminal region of P2-initiated mRNA was characterized by ... More
Modulation of Inter-kingdom Communication by PhcBSR Quorum Sensing System in Ralstonia solanacearum Phylotype I Strain GMI1000.
Ralstonia solanacearum is a ubiquitous soil-borne plant pathogenic bacterium, which frequently encounters and interacts with other soil cohabitants in competition for environmental niches. Ralsolamycin, which is encoded by the rmy genes, has been characterized as a novel inter-kingdom interaction signal that induces chlamydospore development in fungi. In this study, we ... More
Parallel in vivo analysis of large-effect autism genes implicates cortical neurogenesis and estrogen in risk and resilience.
Gene ontology analyses of autism spectrum disorders (ASD) risk genes have repeatedly highlighted synaptic function and transcriptional regulation as key points of convergence. However, these analyses rely on incomplete knowledge of gene function across brain development. Here we leverage Xenopus tropicalis to study, in vivo, ten genes with the strongest ... More
Comparison of two cell-free therapeutics derived from adipose tissue: small extracellular vesicles versus conditioned medium.
AuthorsHe C,Dai M,Zhou X,Long J,Tian W,Yu M
JournalStem cell research & therapy
PubMed ID35241142
BACKGROUND: Cell-free therapy has been inspired as a promising approach to overcome the limitations of traditional stem cell therapy. However, the therapeutic effect between extracellular vesicles and conditioned medium with the same source had not been compared. Our previous studies have shown that both the conditioned medium of adipose tissue ... More
Efficacy and Pharmacology of the NLRP3 Inflammasome Inhibitor CP-456,773 (CRID3) in Murine Models of Dermal and Pulmonary Inflammation.
JournalJournal of immunology (Baltimore, Md. : 1950)
PubMed ID27521339
Zika vector transmission risk in temperate Australia: a vector competence study.
AuthorsDuchemin JB,Mee PT,Lynch SE,Vedururu R,Trinidad L,Paradkar P
JournalVirology journal
PubMed ID28599659
BACKGROUND: Zika virus is an emerging pathogen of global importance. It has been responsible for recent outbreaks in the Americas and in the Pacific region. This study assessed five different mosquito species from the temperate climatic zone in Australia and included Aedes albopictus as a potentially invasive species. METHODS: Mosquitoes ... More
Bone morphogenetic protein 9 (BMP9) and BMP10 enhance tumor necrosis factor-α-induced monocyte recruitment to the vascular endothelium mainly via activin receptor-like kinase 2.
Bone morphogenetic proteins 9 and 10 (BMP9/BMP10) are circulating cytokines with important roles in endothelial homeostasis. The aim of this study was to investigate the roles of BMP9 and BMP10 in mediating monocyteâendothelial interactions using an in vitro flow adhesion assay. Herein, we report that whereas BMP9/BMP10 alone had no ... More
Hexokinase 2 promotes tumor growth and metastasis by regulating lactate production in pancreatic cancer.
AuthorsAnderson M,Marayati R,Moffitt R,Yeh JJ
JournalOncotarget
PubMed ID28915575
Pancreatic ductal adenocarcinoma (PDAC) is a KRAS-driven cancer with a high incidence of metastasis and an overall poor prognosis. Previous work in a genetically engineered mouse model of PDAC showed glucose metabolism to be important for maintaining tumor growth. Multiple glycolytic enzymes, including hexokinase 2 (HK2), were upregulated in primary ... More
Integrative genome analysis of somatic p53 mutant osteosarcomas identifies Ets2-dependent regulation of small nucleolar RNAs by mutant p53 protein.
AuthorsPourebrahim R,Zhang Y,Liu B,Gao R,Xiong S,Lin PP,McArthur MJ,Ostrowski MC,Lozano G
JournalGenes & development
PubMed ID29021240
TP53 is the most frequently mutated gene in human cancer. Many mutant p53 proteins exert oncogenic gain-of-function (GOF) properties that contribute to metastasis, but the mechanisms mediating these functions remain poorly defined in vivo. To elucidate how mutant p53 GOF drives metastasis, we developed a traceable somatic osteosarcoma mouse model ... More
Post-translational Modifications of OLIG2 Regulate Glioma Invasion through the TGF-β Pathway.
In glioblastoma, invasion and proliferation are presumed to be mutually exclusive events; however, the molecular mechanisms that mediate this switch at the cellular level remain elusive. Previously, we have shown that phospho-OLIG2, a Central Nervous System-specific transcription factor, is essential for tumor growth and proliferation. Here, we show that modulation ... More
Identification of novel small-molecule inhibitors targeting menin-MLL interaction, repurposing the antidiarrheal loperamide.
Integrative functional analyses using rainbow trout selected for tolerance to plant diets reveal nutrigenomic signatures for soy utilization without the concurrence of enteritis.
AuthorsAbernathy J,Brezas A,Snekvik KR,Hardy RW,Overturf K
JournalPloS one
PubMed ID28723948
Finding suitable alternative protein sources for diets of carnivorous fish species remains a major concern for sustainable aquaculture. Through genetic selection, we created a strain of rainbow trout that outperforms parental lines in utilizing an all-plant protein diet and does not develop enteritis in the distal intestine, as is typical ... More
Suppression of microRNA-144-3p attenuates oxygen-glucose deprivation/reoxygenation-induced neuronal injury by promoting Brg1/Nrf2/ARE signaling.
AuthorsLi Y,Zhao Y,Cheng M,Qiao Y,Wang Y,Xiong W,Yue W
JournalJournal of biochemical and molecular toxicology
PubMed ID29457851
No detriment in taste response or expression in offspring of mice fed representative levels of sucrose or non-caloric sucralose while pregnant.
AuthorsChoo E,Dando R
JournalPhysiology & behavior
PubMed ID29108962
Contributions of the oligopeptide permeases in multistep of Vibrio alginolyticus pathogenesis.
AuthorsLiu W,Huang L,Su Y,Qin Y,Zhao L,Yan Q
JournalMicrobiologyOpen
PubMed ID28714216
Vibrio alginolyticus has been associated with several diseases of cultivated marine animals, and has led to considerable economic losses. The oligopeptide permease (Opp) has been proven to play a variety of important roles in nutrition and virulence in several bacteria. In our previous research, the opp gene cluster was identified ... More
Comparative analysis of molecular signatures suggests the use of gabapentin for the management of endometriosis-associated pain.
BACKGROUND: It has been repetitively shown that the transcription factors DLX5 and DLX6 are drastically downregulated in endometriotic lesions when compared with eutopic endometrium. These findings suggest that regulatory cascades involving DLX5/6 might be at the origin of endometriosis symptoms such as chronic pelvic pain (CPP). We have shown that ... More
Cooperative Regulatory Functions of miR858 and MYB83 during Cyst Nematode Parasitism.
AuthorsPiya S,Kihm C,Rice JH,Baum TJ,Hewezi T
JournalPlant physiology
PubMed ID28512179
MicroRNAs (miRNAs) recently have been established as key regulators of transcriptome reprogramming that define cell function and identity. Nevertheless, the molecular functions of the greatest number of miRNA genes remain to be determined. Here, we report cooperative regulatory functions of miR858 and its MYB83 transcription factor target gene in transcriptome ... More
A missense variant in NCF1 is associated with susceptibility to multiple autoimmune diseases.
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a strong genetic component characterized by autoantibody production and a type I interferon signature(1). Here we report a missense variant (g.74779296G>A; p.Arg90His) in NCF1, encoding the p47(phox) subunit of the phagocyte NADPH oxidase (NOX2), as the putative underlying causal variant ... More
Tumor-derived neomorphic mutations in ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcription network.
Additional sex combs-like 1 (ASXL1) interacts with BRCA1-associated protein 1 (BAP1) deubiquitinase to oppose the polycomb repressive complex 1 (PRC1)-mediated histone H2A ubiquitylation. Germline BAP1 mutations are found in a spectrum of human malignancies, while ASXL1 mutations recurrently occur in myeloid neoplasm and are associated with poor prognosis. Nearly all ... More
An HDAC3-PROX1 corepressor module acts on HNF4α to control hepatic triglycerides.
AuthorsArmour SM,Remsberg JR,Damle M,Sidoli S,Ho WY,Li Z,Garcia BA,Lazar MA
JournalNature communications
PubMed ID28916805
The histone deacetylase HDAC3 is a critical mediator of hepatic lipid metabolism, and liver-specific deletion of HDAC3 leads to fatty liver. To elucidate the underlying mechanism, here we report a method of cross-linking followed by mass spectrometry to define a high-confidence HDAC3 interactome in vivo that includes the canonical NCoRâHDAC3 ... More
Co-overexpression of the Constitutively Active Form of OsbZIP46 and ABA-Activated Protein Kinase SAPK6 Improves Drought and Temperature Stress Resistance in Rice.
AuthorsChang Y,Nguyen BH,Xie Y,Xiao B,Tang N,Zhu W,Mou T,Xiong L
JournalFrontiers in plant science
PubMed ID28694815
Drought is one of the major abiotic stresses threatening rice (Oryza sativa) production worldwide. Drought resistance is controlled by multiple genes, and therefore, a multi-gene genetic engineering strategy is theoretically useful for improving drought resistance. However, the experimental evidence for such a strategy is still lacking. In this study, a ... More
The flavonoid hesperidin exerts anti-photoaging effect by downregulating matrix metalloproteinase (MMP)-9 expression via mitogen activated protein kinase (MAPK)-dependent signaling pathways.
AuthorsLee HJ,Im AR,Kim SM,Kang HS,Lee JD,Chae S
JournalBMC complementary and alternative medicine
PubMed ID29382339
BACKGROUND: Hesperidin is a flavonoid with antioxidant, anti-inflammatory, and immune modulatory activities. Photoaging is a consequence of chronic exposure to the sun and ultraviolet (UV) radiation. This study was designed to evaluate the efficacy of hesperidin against photoaging of dorsal skin in hairless mice. METHODS: Hairless male mice (6-week-old) were ... More
Studies on inflammatory disorders elucidated the pivotal role of the CX3CL1/CX3CR1 axis with respect to the pathophysiology and diseases progression. Coxsackievirus B3 (CVB3)-induced myocarditis is associated with severe cardiac inflammation, which may progress to heart failure. We therefore investigated the influence of CX3CR1 ablation in the model of acute myocarditis, ... More
Isolation and characterization of the fall Chinook aquareovirus.
AuthorsMakhsous N,Jensen NL,Haman KH,Batts WN,Jerome KR,Winton JR,Greninger AL
JournalVirology journal
PubMed ID28870221
BACKGROUND: Salmon are paramount to the economy, ecology, and history of the Pacific Northwest. Viruses constitute one of the major threats to salmon health and well-being, with more than twenty known virus species that infect salmon. Here, we describe the isolation and characterization of the fall Chinook aquareovirus, a divergent ... More
Identification and Bioinformatic Analysis of the GmDOG1-Like Family in Soybean and Investigation of Their Expression in Response to Gibberellic Acid and Abscisic Acid.
Seed germination is one of the most important stages during plant life cycle, and DOG1 (Delay of germination1) plays a pivotal regulatory role in seed dormancy and germination. In this study, we have identified the DOG1-Like (DOG1L) family in soybean (Glycine max), a staple oil crop worldwide, and investigated their ... More
KIF5A transports collagen vesicles of myofibroblasts during pleural fibrosis.
Fibrosis involves the production of extracellular matrix proteins in tissues and is often preceded by injury or trauma. In pleural fibrosis excess collagen deposition results in pleural thickening, increased stiffness and impaired lung function. Myofibroblasts are responsible for increased collagen deposition, however the molecular mechanism of transportation of procollagen containing ... More
Modulation of the biomarkers of inflammation and oxidative stress by ruminant trans fatty acids and dairy proteins in vascular endothelial cells (HUVEC).
AuthorsDa Silva MS,Bilodeau JF,Larose J,Greffard K,Julien P,Barbier O,Rudkowska I
JournalProstaglandins, leukotrienes, and essential fatty acids
PubMed ID29031397
Experimental infection of highly pathogenic avian influenza viruses, Clade 2.3.4.4 H5N6 and H5N8, in Mandarin ducks from South Korea.
Repurposing propranolol as an antitumor agent in von Hippel-Lindau disease.
AuthorsShepard MJ,Bugarini A,Edwards NA,Lu J,Zhang Q,Wu T,Zhuang Z,Chittiboina P
JournalJournal of neurosurgery
PubMed ID30497198
OBJECTIVE: Von Hippel-Lindau disease (VHL) is a tumor predisposition syndrome characterized by CNS hemangioblastomas (HBs) and clear cell renal cell carcinomas (RCCs) due to hypoxia-inducible factor activation (pseudohypoxia). Because of the lack of effective medical therapies for VHL, HBs and RCCs account for significant morbidity and mortality, ultimately necessitating numerous ... More
Zika virus preferentially replicates in the female reproductive tract after vaginal inoculation of rhesus macaques.
Zika virus (ZIKV) is a mosquito-transmitted virus that can cause severe defects in an infected fetus. ZIKV is also transmitted by sexual contact, although the relative importance of sexual transmission is unclear. To better understand the role of sexual transmission in ZIKV pathogenesis, a nonhuman primate (NHP) model of vaginal ... More
Nrf2-dependent induction of innate host defense via heme oxygenase-1 inhibits Zika virus replication.
AuthorsHuang H,Falgout B,Takeda K,Yamada KM,Dhawan S
JournalVirology
PubMed ID28068513
We identified primary human monocyte-derived macrophages (MDM) as vulnerable target cells for Zika virus (ZIKV) infection. We demonstrate dramatic effects of hemin, the natural inducer of the heme catabolic enzyme heme oxygenase-1 (HO-1), in the reduction of ZIKV replication in vitro. Both LLC-MK2 monkey kidney cells and primary MDM exhibited ... More
Type I interferons suppress viral replication but contribute to T cell depletion and dysfunction during chronic HIV-1 infection.
AuthorsCheng L,Yu H,Li G,Li F,Ma J,Li J,Chi L,Zhang L,Su L
JournalJCI insight
PubMed ID28614789
The direct link between sustained type I interferon (IFN-I) signaling and HIV-1âinduced immunopathogenesis during chronic infection remains unclear. Here we report studies using a monoclonal antibody to block IFN-α/β receptor 1 (IFNAR1) signaling during persistent HIV-1 infection in humanized mice (hu-mice). We discovered that, during chronic HIV-1 infection, IFNAR blockade ... More
Vertebrate-like CRYPTOCHROME 2 from monarch regulates circadian transcription via independent repression of CLOCK and BMAL1 activity.
AuthorsZhang Y,Markert MJ,Groves SC,Hardin PE,Merlin C
JournalProceedings of the National Academy of Sciences of the United States of America
PubMed ID28831003
Circadian repression of CLOCK-BMAL1 by PERIOD and CRYPTOCHROME (CRY) in mammals lies at the core of the circadian timekeeping mechanism. CRY repression of CLOCK-BMAL1 and regulation of circadian period are proposed to rely primarily on competition for binding with coactivators on an α-helix located within the transactivation domain (TAD) of ... More
Mapping of a major QTL for salt tolerance of mature field-grown maize plants based on SNP markers.
BACKGROUND: Salt stress significantly restricts plant growth and production. Maize is an important food and economic crop but is also a salt sensitive crop. Identification of the genetic architecture controlling salt tolerance facilitates breeders to select salt tolerant lines. However, the critical quantitative trait loci (QTLs) responsible for the salt ... More
Transcriptional regulatory dynamics drive coordinated metabolic and neural response to social challenge in mice.
Agonistic encounters are powerful effectors of future behavior, and the ability to learn from this type of social challenge is an essential adaptive trait. We recently identified a conserved transcriptional program defining the response to social challenge across animal species, highly enriched in transcription factor (TF), energy metabolism, and developmental ... More
The mutation of BCOR is highly recurrent and oncogenic in mature T-cell lymphoma.
AuthorsKang JH,Lee SH,Lee J,Choi M,Cho J,Kim SJ,Kim WS,Ko YH,Yoo HY
JournalBMC cancer
PubMed ID33468080
BACKGROUND: BCOR acts as a corepressor of BCL6, a potent oncogenic protein in cancers of the lymphoid lineage. We have found the recurrent somatic mutation of BCOR occurred in mature T-cell lymphoma (TCL). The role of BCOR mutation in lymphoid malignancies is unknown. METHODS: Lymphoma patient samples were analyzed to ... More
Impact of Minocycline on Extracellular Matrix Metalloproteinase Inducer, a Factor Implicated in Multiple Sclerosis Immunopathogenesis.
JournalJournal of immunology (Baltimore, Md. : 1950)
PubMed ID27733550
Identification of lineage-specifying cytokines that signal all CD8(+)-cytotoxic-lineage-fate 'decisions' in the thymus.
AuthorsEtzensperger R,Kadakia T,Tai X,Alag A,Guinter TI,Egawa T,Erman B,Singer A
JournalNature immunology
PubMed ID28945245
T cell antigen receptor (TCR) signaling in the thymus initiates positive selection but CD8 lineage fate is thought to be induced by cytokines after TCR signaling has ceased, although this remains controversial and unproven. We now identify four non-common gamma chain (γc) receptor-signaling cytokines (IL-6, IFN-γ, TSLP, TGF-β) that, like ... More
Development of Potent Type I Protein Arginine Methyltransferase (PRMT) Inhibitors of Leukemia Cell Proliferation.
Activation of Lineage Regulators and Transposable Elements across a Pluripotent Spectrum.
AuthorsHackett JA,Kobayashi T,Dietmann S,Surani MA
JournalStem cell reports
PubMed ID28591649
Embryonic stem cells (ESCs) are characterized by the pluripotent capacity to generate all embryonic lineages. Here, we show that ESCs can occupy a spectrum of distinct transcriptional and epigenetic states in response to varied extrinsic conditions. This spectrum broadly corresponds to a developmental continuum of pluripotency and is coupled with ... More
Divergence of the Floral A-Function between an Asterid and a Rosid Species.
The ABC model is widely used as a genetic framework for understanding floral development and evolution. In this model, the A-function is required for the development of sepals and petals and to antagonize the C-function in the outer floral whorls. In the rosid species Arabidopsis thaliana, the AP2-type AP2 transcription ... More
Injury promotes sarcoma development in a genetically and temporally restricted manner.
Cancer results from the accumulation of genetic mutations in a susceptible cell of origin. We and others have also shown that injury promotes sarcoma development, but how injury cooperates with genetic mutations at the earliest stages of tumor formation is not known. Here, we utilized dual recombinase technology to dissect ... More
Physcomitrella Patens Dehydrins (PpDHNA and PpDHNC) Confer Salinity and Drought Tolerance to Transgenic Arabidopsis Plants.
AuthorsLi Q,Zhang X,Lv Q,Zhu D,Qiu T,Xu Y,Bao F,He Y,Hu Y
JournalFrontiers in plant science
PubMed ID28798765
Dehydrins (DHNs) as a member of late-embryogenesis-abundant (LEA) proteins are involved in plant abiotic stress tolerance. Two dehydrins PpDHNA and PpDHNC were previously characterized from the moss Physcomitrella patens, which has been suggested to be an ideal model plant to study stress tolerance due to its adaptability to extreme environment. ... More
MicroRNAs 218a-5p, 219a-5p, and 221-3p regulate vestibular compensation.
Unilateral vestibular deafferentation (UVD) interrupts afferent signals from one side, resulting in an imbalance of the resting activity between bilateral vestibular nuclei. Vestibular compensation is the process of balancing the resting activity to reestablish homeostasis. Here, we investigated microRNAs (miRNAs) that regulate vestibular compensation using the SpragueâDawley rat. After determining ... More
Improvement of Verticillium Wilt Resistance by Applying Arbuscular Mycorrhizal Fungi to a Cotton Variety with High Symbiotic Efficiency under Field Conditions.
AuthorsZhang Q,Gao X,Ren Y,Ding X,Qiu J,Li N,Zeng F,Chu Z
JournalInternational journal of molecular sciences
PubMed ID29342876
Arbuscular mycorrhizal fungi (AMF) play an important role in nutrient cycling processes and plant stress resistance. To evaluate the effect of Rhizophagus irregularis CD1 on plant growth promotion (PGP) and Verticillium wilt disease, the symbiotic efficiency of AMF (SEA) was first investigated over a range of 3% to 94% in ... More
The detection and stability of the SARS-CoV-2 RNA biomarkers in wastewater influent in Helsinki, Finland.
Wastewater-based surveillance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is used to monitor the population-level prevalence of the COVID-19 disease. In many cases, due to lockdowns or analytical delays, the analysis of wastewater samples might only be possible after prolonged storage. In this study, the effect of storage ... More
A small cassette enables conditional gene inactivation by CRISPR/Cas9.
AuthorsGuzzardo PM,Rashkova C,Dos Santos RL,Tehrani R,Collin P,Bürckstümmer T
JournalScientific reports
PubMed ID29196747
The availability of CRISPR/Cas9 technology has enabled the rapid establishment of gene knockouts in many cell types and even whole organisms. However, conditional inactivation of essential genes remains a challenge. We devised an approach named DECAI (DEgradation based on Cre-regulated- Artificial Intron). It utilizes a small cassette of just 201 ... More
Manipulation of a Senescence-Associated Gene Improves Fleshy Fruit Yield.
Senescence is the process that marks the end of a leafâs lifespan. As it progresses, the massive macromolecular catabolism dismantles the chloroplasts and, consequently, decreases the photosynthetic capacity of these organs. Thus, senescence manipulation is a strategy to improve plant yield by extending the leafâs photosynthetically active window of time. ... More
Prostate Cancer Peripheral Blood NK Cells Show Enhanced CD9, CD49a, CXCR4, CXCL8, MMP-9 Production and Secrete Monocyte-Recruiting and Polarizing Factors.
Natural killer (NK) cells, effector lymphocytes of the innate immunity, have been shown to be altered in several cancers, both at tissue and peripheral levels. We have shown that in Non-Small Cell Lung Cancer (NSCLC) and colon cancer, tumour associated circulating NK (TA-NK) and tumour infiltrating NK (TI-NK) exhibit pro-angiogenic ... More
Discovery of novel BET inhibitors by drug repurposing of nitroxoline and its analogues.
Rice OsLHT1 Functions in Leaf-to-Panicle Nitrogen Allocation for Grain Yield and Quality.
AuthorsGuo N,Gu M,Hu J,Qu H,Xu G
JournalFrontiers in plant science
PubMed ID32849708
Proper allocation of nitrogen (N) from source leaves to grains is essential step for high crop grain yield and N use efficiency. In rice (Oryza sativa) grown in flooding paddy field, amino acids are the major N compounds for N distribution and re-allocation. We have recently identified that Lysine-Histidine-type Transporter ... More
Identification and Functional Characterization of Tomato CircRNAs Derived from Genes Involved in Fruit Pigment Accumulation.
AuthorsTan J,Zhou Z,Niu Y,Sun X,Deng Z
JournalScientific reports
PubMed ID28819222
CircRNAs, a class of widespread circular RNAs produced from precursor mRNA back-splicing, have been implicated in regulation of gene expression in eukaryotes, but their biological functions in plants have not yet been elucidated. By deep sequencing of rRNA-removed and RNase R-digested RNA samples we have identified several thousands of putative ... More
High Expression of Cry1Ac Protein in Cotton (Gossypium hirsutum) by Combining Independent Transgenic Events that Target the Protein to Cytoplasm and Plastids.
AuthorsSingh AK,Paritosh K,Kant U,Burma PK,Pental D
JournalPloS one
PubMed ID27391960
Transgenic cotton was developed using two constructs containing a truncated and codon-modified cry1Ac gene (1,848 bp), which was originally characterized from Bacillus thuringiensis subspecies kurstaki strain HD73 that encodes a toxin highly effective against many lepidopteran pests. In Construct I, the cry1Ac gene was cloned under FMVde, a strong constitutively ... More
Transcriptome analysis of hypoxic cancer cells uncovers intron retention in EIF2B5 as a mechanism to inhibit translation.
Cells adjust to hypoxic stress within the tumor microenvironment by downregulating energy-consuming processes including translation. To delineate mechanisms of cellular adaptation to hypoxia, we performed RNA-Seq of normoxic and hypoxic head and neck cancer cells. These data revealed a significant down regulation of genes known to regulate RNA processing and ... More
Antiobesity and antidiabetic effects of the dairy bacterium Propionibacterium freudenreichii MJ2 in high-fat diet-induced obese mice by modulating lipid metabolism.
AuthorsAn M,Park YH,Lim YH
JournalScientific reports
PubMed ID33510408
Obesity can cause chronic metabolic disorders such as type 2 diabetes, hyperlipidemia, and nonalcoholic fatty liver diseases. The aim of this study was to investigate the antiobesity and antidiabetic effects of the dairy bacterium P. freudenreichii MJ2 isolated from raw milk using 3T3-L1 cells and high-fat diet (HFD)-induced obese mice. ... More
Mapping the cellular response to electron transport chain inhibitors reveals selective signaling networks triggered by mitochondrial perturbation.
Authorsvan der Stel W,Yang H,Vrijenhoek NG,Schimming JP,Callegaro G,Carta G,Darici S,Delp J,Forsby A,White A,le Dévédec S,Leist M,Jennings P,Beltman JB,van de Water B,Danen EHJ
JournalArchives of toxicology
PubMed ID34642769
Mitochondrial perturbation is a key event in chemical-induced organ toxicities that is incompletely understood. Here, we studied how electron transport chain (ETC) complex I, II, or III (CI, CII and CIII) inhibitors affect mitochondrial functionality, stress response activation, and cell viability using a combination of high-content imaging and TempO-Seq in ... More
Cytoplasmic cleavage of DPPA3 is required for intracellular trafficking and cleavage-stage development in mice.
Degradation of maternal proteins by the ubiquitin-proteasome system (UPS) accompanies the maternal-to-zygotic transition. DPPA3/Stella/PGC7, encoded by a maternal effect gene, is present in the nucleus and cytoplasm of zygotes and has been associated with protecting the female pronucleus from TET3-mediated demethylation. We now report that cytoplasmic DPPA3 is partially cleaved ... More
Deletion of a Pathogenic Mutation-Containing Exon of COL7A1 Allows Clonal Gene Editing Correction of RDEB Patient Epidermal Stem Cells.
AuthorsMencía Á,Chamorro C,Bonafont J,Duarte B,Holguin A,Illera N,Llames SG,Escámez MJ,Hausser I,Del Río M,Larcher F,Murillas R
JournalMolecular therapy. Nucleic acids
PubMed ID29858091
Recessive dystrophic epidermolysis bullosa is a severe skin fragility disease caused by loss of functional type VII collagen at the dermal-epidermal junction. A frameshift mutation in exon 80 of COL7A1 gene, c.6527insC, is highly prevalent in the Spanish patient population. We have implemented gene-editing strategies for COL7A1 frame restoration by ... More
Oxidative Stress, DNA Damage and DNA Repair in Female Patients with Diabetes Mellitus Type 2.
BACKGROUND: Diabetes mellitus type 2 (T2DM) is associated with oxidative stress which in turn can lead to DNA damage. The aim of the present study was to analyze oxidative stress, DNA damage and DNA repair in regard to hyperglycemic state and diabetes duration. METHODS: Female T2DM patients (n = 146) ... More
Genetically engineered human cortical spheroid models of tuberous sclerosis.
AuthorsBlair JD,Hockemeyer D,Bateup HS
JournalNature medicine
PubMed ID30127391
Tuberous Sclerosis Complex (TSC) is a multi-system developmental disorder caused by mutations in the TSC1 or TSC2 genes, whose protein products are negative regulators of mTOR complex 1 signaling. Hallmark pathologies of TSC are cortical tubers; regions of dysmorphic, disorganized neurons and glia in the cortex that are linked to ... More
Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia.
Expression of the Ret receptor tyrosine kinase is a defining feature of enteric neurons. Its importance is underscored by the effects of its mutation in Hirschsprung disease, leading to absence of gut innervation and severe gastrointestinal symptoms. We report a new and physiologically significant site of Ret expression in the ... More
Low Blue Light Enhances Phototropism by Releasing Cryptochrome1-Mediated Inhibition of PIF4 Expression.
Shade-avoiding plants, including Arabidopsis (Arabidopsis thaliana), display a number of growth responses, such as elongation of stem-like structures and repositioning of leaves, elicited by shade cues, including a reduction in the blue and red portions of the solar spectrum and a low-red to far-red ratio. Shade also promotes phototropism of ... More