Biomarkers

  • Article
    | Open Access

    The extracellular matrix is under variable strain, but we lack the tools to detect differences in strain. Here the authors develop a probe based on a bacterial fibronectin-binding peptide that binds to relaxed fibronectin fibrils and detects relaxed matrix in cell culture, tissue slices and in vivo.

    • Simon Arnoldini
    • , Alessandra Moscaroli
    •  & Viola Vogel
  • Article
    | Open Access

    The authors use an integrative clustering approach to identify two laryngeal cancer clusters with distinct prognosis and show that mutations damaging the NSD1 and NSD2 methyltransferases segregate to the cluster with favorable prognosis, and independently predict longer survival in patients with laryngeal, but not other head and neck cancers.

    • Suraj Peri
    • , Evgeny Izumchenko
    •  & Erica A. Golemis
  • Article
    | Open Access

    The current FDA-approved whole blood stabilization method for circulating tumor cell (CTC) isolation suffers from RNA degradation. Here the authors combine hypothermic preservation and antiplatelet strategies to stabilize whole blood up to 72 h without compromising CTC yield and RNA integrity.

    • Keith H. K. Wong
    • , Shannon N. Tessier
    •  & Mehmet Toner
  • Article
    | Open Access

    CD4+ T cells secreting interleukin-17 (TH17) have diverse functions in modulating autoimmune diseases. Here the authors show via transcriptome analyses that a subset of human TH 17 co-expressing interferon-γ (TH1/17) has a molecular signature similar to “pathogenic” mouse TH 17 but distinct from “non-pathogenic” mouse TH 17.

    • Dan Hu
    • , Samuele Notarbartolo
    •  & Howard L. Weiner
  • Article
    | Open Access

    Abnormal levels of Aβ42 in the cerebrospinal fluid occur prior to a positive amyloid PET scan in the brain of individuals with Alzheimer’s disease and here the authors use this temporal pattern to identify individuals with very early stage AD. They show that Aβ fibrils start to accumulate in some of the regions of the default mode network and affect brain connectivity before neurodegeneration occurs.

    • Sebastian Palmqvist
    • , Michael Schöll
    •  & Oskar Hansson
  • Article
    | Open Access

    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 Access

    In prostate cancer, the role of mutations in the maternally-inherited mitochondrial genome are not well known. Here, the authors demonstrate frequent, age-dependent mitochondrial mutation in prostate cancer. Strong links between mitochondrial and nuclear mutational profiles are associated with clinical aggressivity.

    • Julia F. Hopkins
    • , Veronica Y. Sabelnykova
    •  & Paul C. Boutros
  • Article
    | Open Access

    Caloric restriction has been shown to increase lifespan in mammals. Here, the authors provide evidence that age-related methylation drift correlates with lifespan and that caloric restriction in mice and rhesus monkeys results in attenuation of age-related methylation drift.

    • Shinji Maegawa
    • , Yue Lu
    •  & Jean-Pierre J. Issa
  • Article
    | Open Access

    Real-time monitoring of phosphate metabolism and distribution in the live body without ionizing radiation is highly desirable. Here, the authors show dissolution-dynamic nuclear polarization technology can enable nuclear magnetic resonance detection of hyperpolarized 31P of important biological phosphates in aqueous solutions.

    • Atara Nardi-Schreiber
    • , Ayelet Gamliel
    •  & Rachel Katz-Brull
  • Article
    | Open Access

    Early detection of gum inflammation caused by dental implants helps prevent tissue damage. Here, the authors present a peptide sensor that generates a bitter taste when cleaved by proteases present in peri-implant disease, embed it in a chewing gum, and compare the probe to existing sensors using patient saliva.

    • J. Ritzer
    • , T. Lühmann
    •  & L. Meinel
  • Article
    | Open Access

    Preparation of samples for diagnosis can affect the detection of biomarkers and metabolites. Here, the authors use a silver nanoparticle plasmonics approach for the detection of biomarkers in patients as well as investigate the distribution of drugs in serum and cerebral spinal fluid.

    • Lin Huang
    • , Jingjing Wan
    •  & Kun Qian
  • Article
    | Open Access

    Predicting the hepatotoxic effects of new drugs is still a challenge. Using toxicogenomics data, the authors here define a predictive toxicogenomic space (PTGS), the component gene space capturing dose-dependent cytotoxicity, and demonstrate that it can be used to accurately predict drug-induced liver pathology, including human drug-induced liver injury fromin vitrodata.

    • Pekka Kohonen
    • , Juuso A. Parkkinen
    •  & Roland C. Grafström
  • Article
    | Open Access

    Sleep patterns vary and are associated with health and disease. Here Purcellet alcharacterize sleep spindle activity in 11,630 individuals and describe age-related changes, genetic influences, and possible confounding effects, serving as a resource for further understanding the physiology of sleep.

    • S. M. Purcell
    • , D. S. Manoach
    •  & R. Stickgold
  • Article
    | Open Access

    Cancer cells adapt to the changing microenvironment by activating different pathways through multiple mechanisms. Here the authors identify long noncoding RNAMIR31HGas a HIF-1α co-activator required for the induction of the hypoxic response and show its oncogenic role in oral carcinogenesis.

    • Jing-Wen Shih
    • , Wei-Fan Chiang
    •  & Hsing-Jien Kung
  • Article
    | Open Access

    Some cancers with DNA mismatch repair deficiency display microsatellite instability. Here the authors analyse twenty three cancer types at the exome and whole-genome level, and identify loci with recurrent microsatellite instability that could be used to identify patients who would benefit from immunotherapy.

    • Isidro Cortes-Ciriano
    • , Sejoon Lee
    •  & Peter J. Park
  • Article
    | Open Access

    Antidepressant drugs are the most common treatment for depressive episodes but only a fraction of patients experience adequate response. Here the authors find dysregulation of miRNAs in peripheral blood samples from depressed patients after antidepressant treatment, and show that the miRNAs are regulators of psychiatrically relevant signalling pathways.

    • Juan Pablo Lopez
    • , Laura M. Fiori
    •  & Gustavo Turecki
  • Article
    | Open Access

    DNA methylation is modulated by environmental factors and has a role in many complex diseases. Here, the authors find that methylation at specific DNA sites is associated with all-cause mortality, and a methylation-based risk score may be informative for risk assessment and stratification.

    • Yan Zhang
    • , Rory Wilson
    •  & Hermann Brenner
  • Article
    | Open Access

    Some adolescents seek novelty, but it is unknown whether the brain circuits underlying this behaviour can be used to predict later, problematic behaviour. Here, authors show that diminished ventral striatal and prefrontal activity in response to anticipated rewards at age 14 in these individuals predicts problematic drug use at age 16.

    • Christian Büchel
    • , Jan Peters
    •  & Veronika Ziesch
  • Article
    | Open Access

    Pain is affected by cerebral processes in addition to afferent nociceptive input. Here the authors develop an fMRI-based signature that predicts pain independent of the intensity of nociceptive signals and mediates the pain-modulating effects of several cognitive interventions.

    • Choong-Wan Woo
    • , Liane Schmidt
    •  & Tor D. Wager
  • Article
    | Open Access

    The heterogeneity of colorectal cancer has important clinical and therapeutic implications. Here the authors analysed the responses of a large biobank of organoids and xenografts derived from colorectal patients to a panel of clinically relevant therapeutic agents to identify genes signatures associated with drug response.

    • Moritz Schütte
    • , Thomas Risch
    •  & Marie-Laure Yaspo
  • Article
    | Open Access

    The rat is a widely-used model for human biology, but we must be aware of metabolic differences. Here, the authors reconstruct the genome-scale metabolic network of the rat, and after reconciling it with an improved human metabolic model, demonstrate the power of the models to integrate toxicogenomics data, providing species-specific biomarker predictions in response to a panel of drugs.

    • Edik M. Blais
    • , Kristopher D. Rawls
    •  & Jason A. Papin
  • Article
    | Open Access

    ATM is a tumor suppressor often mutated in lung adenocarcinoma. In this study, the authors starting from a synthetic lethal screen, demonstrate that tumor cells with mutations in ATM exhibit increased sensitivity to MEK1/2 inhibition through the modulation of the AKT/mTOR pathway.

    • Michal Smida
    • , Ferran Fece de la Cruz
    •  & Sebastian M. B. Nijman
  • Article
    | Open Access

    Whether Alzheimer’s disease originates in basal forebrain or entorhinal cortex remains highly debated. Here the authors use structural magnetic resonance data from a longitudinal sample of participants stratified by cerebrospinal biomarker and clinical diagnosis to show that tissue volume changes appear earlier in the basal forebrain than in the entorhinal cortex.

    • Taylor W. Schmitz
    • , R. Nathan Spreng
    •  & Ansgar J. Furst
  • Article
    | Open Access

    Sensitive and label-free imaging methods to visualize nerve degeneration are currently lacking. Here authors show that stimulated Raman scattering (SRS) microscopy can be used to monitor peripheral nerve degeneration in mouse models of amyotrophic lateral sclerosis (ALS) and in postmortem tissue from ALS patients.

    • Feng Tian
    • , Wenlong Yang
    •  & Kevin Eggan
  • Article
    | Open Access

    NAD+ is an important coenzyme that mediates cellular metabolism and defends against stresses due to age and overnutrition. Here the authors demonstrate unique bioavailability of the NAD+ precursor vitamin nicotinamide riboside (NR) in mice and humans, and show that NR safely elevates human NAD+.

    • Samuel A. J. Trammell
    • , Mark S. Schmidt
    •  & Charles Brenner
  • Article
    | Open Access

    BRAF inhibitors often show skin-hyperproliferative side effects in melanoma patients. Here, the authors demonstrate that BRAF inhibitors can be used to enhance skin wound healing through the MAPK- ERK pathway activation that positively regulates the proliferation of keratinocytes.

    • Helena Escuin-Ordinas
    • , Shuoran Li
    •  & Antoni Ribas
  • Article
    | Open Access

    A tumour’s cell of origin may influence tumour progression and response to therapy. Here, the authors demonstrate that the cell of origin determines the aggressiveness of AML in a mouse model and identify unique biomarkers of the specific leukaemia cell of origin by profiling open chromatin regions of AML samples.

    • Joshy George
    • , Asli Uyar
    •  & Jennifer J. Trowbridge
  • Article
    | Open Access

    The eIF4E-binding proteins (4E-BPs) are critical repressors of cap-dependent translation via mTOR, a pathway frequently hyperactivated in cancer. Here the authors show that 4E-BP3 specifically mediates the cap-dependent translation repression and antiproliferative effects of prolonged pharmacological mTOR inhibition.

    • Yoshinori Tsukumo
    • , Tommy Alain
    •  & Nahum Sonenberg
  • Article
    | Open Access

    Exosomes are RNA-containing lipid vesicles with roles in inter-tissue crosstalk. Here the authors show that exosome release from brown adipocytes is increased upon thermogenic activation, both in vitro and in vivo, and demonstrate that serum levels of exosomal miR-92 reflect brown fat activity in humans.

    • Yong Chen
    • , Joschka J. Buyel
    •  & Alexander Pfeifer
  • Article
    | Open Access

    Aging is associated with impaired pancreatic islet function, increased risk of type 2 diabetes, and changes in DNA methylation. Here the authors find blood-based biomarkers that reflect age-associated DNA methylation changes in human pancreatic islets associated with insulin secretion and diabetes.

    • Karl Bacos
    • , Linn Gillberg
    •  & Charlotte Ling
  • Article
    | Open Access

    Regenerative tissue engineering with mesenchymal stem cells is hampered by bulk methods of assessing differentiation status and a general assumption that expression of individual markers of stem cell differentiation correlate with functional capacity. Here the authors debunk this assumption by applying single-cell techniques to disassociate aggrecan mRNA abundance and matrix deposition.

    • Allison J. Cote
    • , Claire M. McLeod
    •  & Robert L. Mauck
  • Article
    | Open Access

    Acquired resistance to anti-angiogenic drugs, including bevacizumab, may occur in cancer patients. In this study the authors identify in the tumour microenvironment, fibrocyte-like cells derived from the bone marrow that mediate the resistance to bevacizumab through the production of FGF2.

    • Atsushi Mitsuhashi
    • , Hisatsugu Goto
    •  & Yasuhiko Nishioka
  • Article
    | Open Access

    DNA circulating in the plasma of cancer patients carries features of the primary tumour, however such DNA is found in low levels in brain cancer patients. Here, the authors show that circulating tumour DNA can be detected in the cerebral spinal fluid of cancer patients and that this better recapitulates the primary tumour compared to DNA from the plasma.

    • Leticia De Mattos-Arruda
    • , Regina Mayor
    •  & Joan Seoane
  • Article
    | Open Access

    In some HIV-1-infected individuals, viraemia remains undetectable after antiretroviral treatment, but which of these patients will experience viral rebound is difficult to predict. Here the authors show that T cell exhaustion markers before treatment are predictive of shorter time to viral rebound.

    • Jacob Hurst
    • , Matthias Hoffmann
    •  & John Frater
  • Article
    | Open Access

    Chemokines and their receptors have key roles in tumorigenesis. Here, the authors demonstrate that CXRC4 is overexpressed in hepatocellular carcinoma and is associated with poor prognosis and, mechanistically CXCR4 is increased in expression via EZH2 repression of microRNA-622.

    • Haiou Liu
    • , Yidong Liu
    •  & Jiejie Xu
  • Article
    | Open Access

    IL6-STAT3 signaling is activated in prostate cancer, however inhibiting this pathway has not lead to a survival advantage in patients. Here, Pencik et al.show that loss of the IL6-STAT3 axis in mice and humans leads to metastasis due to loss of ARF, unravelling STAT3 and ARF as potential prognostic markers in prostate cancer.

    • Jan Pencik
    • , Michaela Schlederer
    •  & Lukas Kenner
  • Article
    | Open Access

    Immune thrombocytopenia (ITP) is caused by autoantibody-mediated platelet clearance, but refractoriness to current immunomodulatory therapies is common. Here the authors show that desialylated platelets can be cleared via hepatic Ashwell–Morell receptor, a process that can be attenuated by sialidase inhibitors, suggesting a new therapy for ITP.

    • June Li
    • , Dianne E. van der Wal
    •  & Heyu Ni