8,128 results match your criteria: "Koch Institute[Affiliation]"

An association of mental health and in particular depression with cardiovascular disease has been shown in adults and to a lesser extent in the young. Recently improved measurement methods of carotid-intima media thickness (CIMT) and carotid stiffness (CS) allow more differentiated analyses of this link. We examined 4,361 participants of the nationwide KiGGS cohort aged 3-17 years at baseline and 14-28 years at follow-up.

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Cancer immune evasion, immunoediting and intratumour heterogeneity.

Nat Rev Immunol

January 2025

Koch Institute for Integrative Cancer Research, Massachusetts Institute for Technology, Cambridge, MA, USA.

Cancers can avoid immune-mediated elimination by acquiring traits that disrupt antitumour immunity. These mechanisms of immune evasion are selected and reinforced during tumour evolution under immune pressure. Some immunogenic subclones are effectively eliminated by antitumour T cell responses (a process known as immunoediting), which results in a clonally selected tumour.

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Intradermal Bacillus Calmette-Guérin (BCG) is the most widely administered vaccine, but it does not sufficiently protect adults against pulmonary tuberculosis. Recent studies in nonhuman primates show that intravenous BCG administration offers superior protection against (). We used single-cell analysis of bronchoalveolar lavage cells from rhesus macaques vaccinated via different routes and doses of BCG to identify alterations in the immune ecosystem in the airway following vaccination.

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Background: In Europe, the health situation is primarily influenced by non-communicable diseases. Comparable information on key indicators for the European region can highlight potential areas for improvement in prevention and care.

Method: Based on EHIS 3, age-standardised prevalences of three disease groups and two indicators of self-assessed health among those affected were presented for Germany ( = 22,708) and the average of 29 European countries ( = 301,960).

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Background: Needs-based care is a central concern of healthcare policy. A European comparison of the utilisation of medical services can help to assess national data and identify the need for action.

Methods: This article describes indicators on the utilisation of outpatient and inpatient services, medical examinations and the use of medicines from the third wave of the European Health Interview Survey (EHIS 3) and compares the results from Germany with the European averages.

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Pneumococcal infections are a serious health issue associated with increased morbidity and mortality. This systematic review evaluated the efficacy, effectiveness, immunogenicity, and safety of the pneumococcal conjugate vaccine (PCV)15 compared to other pneumococcal vaccines or no vaccination in children and adults. We identified 20 randomized controlled trials (RCTs).

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Introduction: Accurate and consistent data play a critical role in enabling health officials to make informed decisions regarding emerging trends in SARS-CoV-2 infections. Alongside traditional indicators such as the 7-day-incidence rate, wastewater-based epidemiology can provide valuable insights into SARS-CoV-2 concentration changes. However, the wastewater compositions and wastewater systems are rather complex.

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Lymphatic muscle cells (LMCs) within the wall of collecting lymphatic vessels exhibit tonic and autonomous phasic contractions, which drive active lymph transport to maintain tissue-fluid homeostasis and support immune surveillance. Damage to LMCs disrupts lymphatic function and is related to various diseases. Despite their importance, knowledge of the gene transcriptional signatures in LMCs and how they relate to lymphatic function in normal and disease contexts is largely missing.

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The T cell receptor sequence influences the likelihood of T cell memory formation.

Cell Rep

January 2025

Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address:

The amino acid sequence of the T cell receptor (TCR) varies between T cells of an individual's immune system. Particular TCR residues nearly guarantee mucosal-associated invariant T (MAIT) and natural killer T (NKT) cell transcriptional fates. To define how the TCR sequence affects T cell fates, we analyze the paired αβTCR sequence and transcriptome of 961,531 single cells.

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Effects of Aging on Glucose and Lipid Metabolism in Mice.

Aging Cell

December 2024

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

Article Synopsis
  • Aging leads to cellular damage and mitochondrial dysfunction, impacting metabolism and contributing to age-related diseases.
  • The cofactor NAD decreases in tissues with age and is crucial for various metabolic pathways, yet its levels and ratio to NADH remained stable during healthy aging in mice studied.
  • Research showed that older tissues, especially in the brain, increased fatty acid and sphingolipid metabolism, helping to maintain NAD levels, which could be essential for healthy aging.
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Modulating cell-free DNA biology as the next frontier in liquid biopsies.

Trends Cell Biol

December 2024

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

Technical advances over the past two decades have enabled robust detection of cell-free DNA (cfDNA) in biological samples. Yet, higher clinical sensitivity is required to realize the full potential of liquid biopsies. This opinion article argues that to overcome current limitations, the abundance of informative cfDNA molecules - such as circulating tumor DNA (ctDNA) - collected in a sample needs to increase.

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Heparan sulfate regulates the fate decisions of human pluripotent stem cells.

Stem Cell Reports

January 2025

Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, USA; Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, USA; Koch Institute for Integrative Cancer Research at MIT, 500 Main St, Cambridge, MA 02142, USA. Electronic address:

Heparan sulfate (HS) is an anionic polysaccharide generated by all animal cells, but our understanding of its roles in human pluripotent stem cell (hPSC) self-renewal and differentiation is limited. We derived HS-deficient hPSCs by disrupting the EXT1 glycosyltransferase. These EXT1 hPSCs maintain self-renewal and pluripotency under standard culture conditions that contain high levels of basic fibroblast growth factor(bFGF), a requirement for sufficient bFGF signaling in the engineered cells.

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Background: Universal lipid screening in childhood for early detection and treatment of familial hypercholesterolemia is under discussion, but will also detect children with multifactorial dyslipidemia. Results from population-based studies can support the design of public health strategies. As few previous studies considered pubertal changes in serum lipid levels, we examined tracking of serum lipids from prepuberty to young adulthood in a population-based cohort.

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Immune reactions to medical implants often lead to encapsulation by fibrotic tissue and impaired device function. This process is thought to initiate by protein adsorption, which enables immune cells to attach and mount an inflammatory response. Previously, several antifibrotic materials have been either designed to reduce protein adsorption or discovered via high-throughput screens (HTS) to favorably regulate inflammation.

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LDB1 establishes multi-enhancer networks to regulate gene expression.

Mol Cell

January 2025

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. Electronic address:

How specific enhancer-promoter pairing is established remains mostly unclear. Besides the CTCF/cohesin machinery, few nuclear factors have been studied for a direct role in physically connecting regulatory elements. Using a murine erythroid cell model, we show via acute degradation experiments that LDB1 directly and broadly promotes connectivity among regulatory elements.

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PairK: Pairwise k-mer alignment for quantifying protein motif conservation in disordered regions.

Protein Sci

January 2025

Department of Biology, MIT, Cambridge, Massachusetts, USA.

Protein-protein interactions are often mediated by a modular peptide recognition domain binding to a short linear motif (SLiM) in the disordered region of another protein. To understand the features of SLiMs that are important for binding and to identify motif instances that are important for biological function, it is useful to examine the evolutionary conservation of motifs across homologous proteins. However, the intrinsically disordered regions (IDRs) in which SLiMs reside evolve rapidly.

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Pooled Nanoparticle Screening Using a Chemical Barcoding Approach.

Angew Chem Int Ed Engl

January 2025

Department of Chemical Engineering and Materials Science, University of Minnesota Twin Cities, Minneapolis, MN, USA.

We report the development of a small molecule-based barcoding platform for pooled screening of nanoparticle delivery. Using aryl halide-based tags (halocodes), we achieve high-sensitivity detection via gas chromatography coupled with mass spectrometry or electron capture. This enables barcoding and tracking of nanoparticles with minimal halocode concentrations and without altering their physicochemical properties.

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Chronic pain can be complicated by problematic opioid use, which may decrease engagement in care and HIV medication adherence. Pain-related anxiety and catastrophic thinking augment pain severity and interference while driving increased substance use. The acceptability and effect of a music-based smartphone application on negative affect and catastrophic thinking were evaluated in a mixed-methods study among persons living with HIV (PWH) with problematic opioid use and chronic pain.

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End-to-end simulation of nanopore sequencing signals with feed-forward transformers.

Bioinformatics

December 2024

Centre for Artificial Intelligence in Public Health Research, Robert Koch Institute, Berlin 13353, Germany.

Motivation: Nanopore sequencing represents a significant advancement in genomics, enabling direct long-read DNA sequencing at the single-molecule level. Accurate simulation of nanopore sequencing signals from nucleotide sequences is crucial for method development and for complementing experimental data. Most existing approaches rely on predefined statistical models, which may not adequately capture the properties of experimental signal data.

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The impact of information and communication technology on immunisation and immunisation programmes in low-income and middle-income countries: a systematic review and meta-analysis.

EBioMedicine

January 2025

Evidence-Based Public Health, Centre for International Health Protection, Robert Koch Institute, Berlin, Germany; Unité Epidémiologie et Recherche Clinique, Réseau de l'Arc, Saint-Imier, Switzerland.

Background: Low-income and Middle-income Countries (LMIC) are continually working to ensure everyone can access life-saving vaccines. Recognising the considerable impact of Information and Communication Technology (ICT) in healthcare, we performed a systematic review and meta-analysis to summarise ICT effectiveness in improving vaccine delivery in LMICs.

Methods: A systematic search from January 2010 to August 2023 in MEDLINE, EMBASE, Cochrane Library, BMJ Health & Care Informatics, and grey literature was performed.

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Deep profiling deconstructs features associated with memory CD8 T cell tissue residence.

Immunity

January 2025

Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:

Tissue-resident memory CD8 T (Trm) cells control infections and cancer and are defined by their lack of recirculation. Because migration is difficult to assess, residence is usually inferred by putative residence-defining phenotypic and gene signature proxies. We assessed the validity and universality of residence proxies by integrating mouse parabiosis, multi-organ sampling, intravascular staining, acute and chronic infection models, dirty mice, and single-cell multi-omics.

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Putative looping factor ZNF143/ZFP143 is an essential transcriptional regulator with no looping function.

Mol Cell

January 2025

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Gene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA. Electronic address:

Interactions between distal loci, including those involving enhancers and promoters, are a central mechanism of gene regulation in mammals, yet the protein regulators of these interactions remain largely undetermined. The zinc-finger transcription factor (TF) ZNF143/ZFP143 has been strongly implicated as a regulator of chromatin interactions, functioning either with or without CTCF. However, how ZNF143/ZFP143 functions as a looping factor is not well understood.

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Background: People who inject drugs (PWID) are at high risk of blood-borne infections, and injection drug use contributes significantly to hepatitis C virus (HCV) transmission. The WHO has therefore set targets of reducing HCV incidence and prevalence among PWID and increasing treatment coverage to eliminate HCV by 2030. The DRUCK study (2011-2014) found high HCV prevalence and low treatment coverage among PWID in Germany.

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Pan-cancer analysis of biallelic inactivation in tumor suppressor genes identifies KEAP1 zygosity as a predictive biomarker in lung cancer.

Cell

December 2024

Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address:

The canonical model of tumor suppressor gene (TSG)-mediated oncogenesis posits that loss of both alleles is necessary for inactivation. Here, through allele-specific analysis of sequencing data from 48,179 cancer patients, we define the prevalence, selective pressure for, and functional consequences of biallelic inactivation across TSGs. TSGs largely assort into distinct classes associated with either pan-cancer (Class 1) or lineage-specific (Class 2) patterns of selection for biallelic loss, although some TSGs are predominantly monoallelically inactivated (Class 3/4).

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