Featured
-
-
Article
| Open AccessThe senescence-associated secretory phenotype is potentiated by feedforward regulatory mechanisms involving Zscan4 and TAK1
In cancer the side effects of therapeutic agents can provoke senescence-associated secretory phenotype (SASP), which can drive cancer resistance. During the DNA damage response, transcription factor Zscan4 expression is elevated by an ATM-TRAF6-TAK1 axis leading to long term SASP in human stromal cells.
- Boyi Zhang
- , Da Fu
- & Yu Sun
-
Article
| Open AccessMotion model ultrasound localization microscopy for preclinical and clinical multiparametric tumor characterization
The vascular structure of tumors impacts diagnosis, prognosis and drug response; however, imaging methods to analyse this important feature have been hindered by spatial resolution limitations. Here the authors present a tool called motion model ultrasound localization microscopy to morphologically and functionally characterize fine vascular networks in tumors at super-resolution.
- Tatjana Opacic
- , Stefanie Dencks
- & Fabian Kiessling
-
Article
| Open AccessChronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults
Declining NAD+ levels have been linked to aging-associated pathologies. Here the authors present results of a double-blind, randomized crossover trial on 30 healthy middle-aged individuals to show that nicotinamide riboside effectively elevates NAD+ levels in humans, appears to be well tolerated, and may have potential to improve cardiovascular parameters.
- Christopher R. Martens
- , Blair A. Denman
- & Douglas R. Seals
-
Article
| Open AccessAdoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells
A critical determinant of tumor eradication by adoptive immunotherapy is the tumor associated antigen recognized by cytotoxic T lymphocytes. Here the authors generate ex vivo autologous cytotoxic T lymphocytes by exposure to antigens induced by DNA demethylation and report the results of a phase 1 trial of 25 patients with recurrent glioblastoma multiforme with tumor regression in three patients.
- Alexei F. Kirkin
- , Karine N. Dzhandzhugazyan
- & Walter Fischer
-
Article
| Open AccessA ligand-specific blockade of the integrin Mac-1 selectively targets pathologic inflammation while maintaining protective host-defense
Integrin-based therapeutics could block inflammatory processes but they also impair host defence, limiting their usefulness. Here the authors report an anti-Mac1 antibody that blocks its interaction with pro-inflammatory ligand CD40L but not other ligands, and show that it can protect against sepsis in mice.
- Dennis Wolf
- , Nathaly Anto-Michel
- & Andreas Zirlik
-
Article
| Open AccessNanoparticle anchoring targets immune agonists to tumors enabling anti-cancer immunity without systemic toxicity
Immunostimulatory agents used in cancer treatment often elicit serious toxicities, limiting their clinical application. Here, the authors show that the use of liposomes to intravenously deliver surface-anchored IL-2 and anti-CD137 proteins enables anti-cancer immunity and reduces the toxic side effects.
- Yuan Zhang
- , Na Li
- & Darrell J. Irvine
-
Article
| Open AccessAnalyses of gut microbiota and plasma bile acids enable stratification of patients for antidiabetic treatment
The authors examine the effects of antidiabetic medication on the gut microbiome and bile acid composition and show that these data can be used to stratify treatment regimens for type 2 diabetes.
- Yanyun Gu
- , Xiaokai Wang
- & Weiqing Wang
-
Article
| Open AccessNon-invasive assessment of hepatic mitochondrial metabolism by positional isotopomer NMR tracer analysis (PINTA)
Liver mitochondrial metabolism plays an important role for glucose and lipid homeostasis and its alterations contribute to metabolic disorders, including fatty liver and diabetes. Here Perry et al. develop a method for the measurement of hepatic fluxes by using lactate and glucose tracers in combination with NMR spectroscopy.
- Rachel J. Perry
- , Liang Peng
- & Gerald I. Shulman
-
Article
| Open AccessMicromotor-enabled active drug delivery for in vivo treatment of stomach infection
Nano- and micromotors have been demonstrated in vitro for a range of applications. Here the authors demonstrate the in-vivo therapeutic use of micromotors to treat H. pylori infection.
- Berta Esteban-Fernández de Ávila
- , Pavimol Angsantikul
- & Joseph Wang
-
Article
| Open AccessA bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice
There is a clinical need to develop a bioengineering system to support ovary transplantation. Here, the authors generate a bioprosthetic ovary using 3D printed scaffolds of varying pore architectures to support follicle survival and ovarian function in sterilized mice.
- Monica M. Laronda
- , Alexandra L. Rutz
- & Ramille N. Shah
-
Article
| Open AccessErythrocytes retain hypoxic adenosine response for faster acclimatization upon re-ascent
Humans that reach high altitude soon after the first ascent show faster adaptation to hypoxia. Songet al. show that this adaptive response relies on decreased red blood cell uptake of plasma adenosine due to reduced levels of nucleoside transporter ENT1 resulting from coordinated adenosine generation by ectonucleotidase CD73 and activation of A2B receptors.
- Anren Song
- , Yujin Zhang
- & Yang Xia
-
Article
| Open AccessDisruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias
Catheter ablation is a common therapy for atrial fibrillation but disrupts cardiac cholinergic neurons. Here the authors report that cholinergic neurons innervate heart ventricles and show that their ablation leads to increased susceptibility to ventricular arrhythmias in mouse models and in patients.
- Christiane Jungen
- , Katharina Scherschel
- & Christian Meyer
-
Article
| Open AccessSemi-automated closed system manufacturing of lentivirus gene-modified haematopoietic stem cells for gene therapy
Current methods for haematopoietic stem cell gene therapy are laborious and require special licensed facilities. Here the authors develop a semi-automated protocol using a commercially available device to allow for benchtop generation of gene-modified blood cell products for transplantation, that meet current standards.
- Jennifer E. Adair
- , Timothy Waters
- & Hans-Peter Kiem
-
Article
| Open AccessA human genome-wide loss-of-function screen identifies effective chikungunya antiviral drugs
Chikungunya virus is a mosquito transmitted untreatable emergent pathogen that causes joint pain and fever. Here the authors perform a host genome-wide loss-of-function screen to identify targets for chikungunya antiviral drugs and validate hits using a mouse model of chikungunya infection.
- Alexander Karlas
- , Stefano Berre
- & Marc Lecuit
-
Article
| Open AccessGenome-wide screening identifies a KCNIP1 copy number variant as a genetic predictor for atrial fibrillation
Tsai et al. here utilize a multi-stage genome-wide association study in Taiwanese population to show a copy number variation in the intron of potassium interacting channel 1 gene (KCNIP1) to be strongly associated with atrial fibrillation. The study also examines the functionality of KCNIP1 in heart electrophysiological function using cultured myocytes and zebrafish.
- Chia-Ti Tsai
- , Chia-Shan Hsieh
- & Jiunn-Lee Lin
-
Article
| Open AccessCritical role of sphingosine-1-phosphate receptor-2 in the disruption of cerebrovascular integrity in experimental stroke
The sphingolipid sphingosine-1-phosphate (S1P) plays a vital role in vascular homeostasis through the interaction with its receptors S1PR1-5. Here, by using genetic and pharmacological approaches, the authors show that S1PR2-mediated signaling is crucial for the disruption of cerebrovascular integrity and development of intracerebral haemorrhage in a mouse stroke model.
- Gab Seok Kim
- , Li Yang
- & Teresa Sanchez
-
Article |
Cryo-electron tomography reveals ciliary defects underlying human RSPH1 primary ciliary dyskinesia
Our current understanding of cilia biology and ciliary diseases is incomplete, in part because cilia are hard to visualize. Here, the authors use cryo-electron tomography to image the structure of human cilia with high resolution and uncover the elusive ciliary defects in Primary Ciliary Dyskinesia patients.
- Jianfeng Lin
- , Weining Yin
- & Daniela Nicastro