3,455 results match your criteria: "Whitehead Institute for Biomedical Research; Cambridge[Affiliation]"

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures.

Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant.

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  • Scientists have found that high-grade serous ovarian cancer (HGSOC) mostly starts in the fallopian tubes instead of the ovaries, but why this happens is still a mystery.
  • The study shows that cells in the fallopian tubes are different from those on the ovarian surface, which helps explain why cancers arise from the tubes.
  • They discovered that these fallopian tube cells have more problems dealing with stress and repairing DNA, and certain genetic factors make the cancer even worse, especially after menopause.
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  • In animals, piRNAs work with PIWI proteins to silence transposons, and in species like Drosophila, these RNAs are passed from mother to offspring to kickstart piRNA production.
  • This research focuses on the Y-linked piRNA locus Su(Ste) in Drosophila, demonstrating that its piRNAs are generated in male germlines and initiated by maternal transposon piRNAs.
  • The study reveals that when XXY mothers deposit Su(Ste) piRNAs, it eliminates the need for sons to produce their own, showcasing a unique way mothers can shield their male offspring through genetic mechanisms.
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The emergence of large language models (LLMs) and assisted artificial intelligence (AI) technologies have revolutionized the way in which we interact with technology. A recent symposium at the Walter and Eliza Hall Institute explored the current practical applications of LLMs in medical research and canvassed the emerging ethical, legal and social implications for the use of AI-assisted technologies in the sciences. This paper provides an overview of the symposium's key themes and discussions delivered by diverse speakers, including early career researchers, group leaders, educators and policy-makers highlighting the opportunities and challenges that lie ahead for scientific researchers and educators as we continue to explore the potential of this cutting-edge and emerging technology.

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Temperature increases as light intensity rises, but whether light signals can be directly linked to high temperature response in plants is unclear. Here, we find that light pre-treatment enables plants to survive better under high temperature, designated as light-induced thermotolerance (LIT). With short-term light treatment, plants induce light-signaling pathway genes and heat shock genes.

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Ferroptosis is a form of regulated cell death with roles in degenerative diseases and cancer. Excessive iron-catalyzed peroxidation of membrane phospholipids, especially those containing the polyunsaturated fatty acid arachidonic acid (AA), is central in driving ferroptosis. Here, we reveal that an understudied Golgi-resident scaffold protein, MMD, promotes susceptibility to ferroptosis in ovarian and renal carcinoma cells in an ACSL4- and MBOAT7-dependent manner.

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Screening in serum-derived medium reveals differential response to compounds targeting metabolism.

Cell Chem Biol

September 2023

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Dana-Farber Cancer Institute, Boston, MA 02115, USA. Electronic address:

A challenge for screening new anticancer drugs is that efficacy in cell culture models is not always predictive of efficacy in patients. One limitation of standard cell culture is a reliance on non-physiological nutrient levels, which can influence cell metabolism and drug sensitivity. A general assessment of how physiological nutrients affect cancer cell response to small molecule therapies is lacking.

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Evaluation of the Potential for Drug Interactions by Salidroside.

Nutrients

August 2023

DoubleRainbow Biosciences Inc., Lexington, MA 02421, USA.

Several studies utilizing , which contains a complex mixture of phytochemicals, reported some positive drug-drug interaction (DDI) findings based on in vitro CYP450's enzyme inhibition, MAO-A and MAO-B inhibition, and preclinical pharmacokinetic studies in either rats or rabbits. However, variation in and multiplicity of constituents present in products is a cause for concern for accurately evaluating drug-drug interaction (DDI) risk. In this report, we examined the effects of bioengineered, nature-identical salidroside on the inhibition potential of salidroside on CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 utilizing human liver microsomes, the induction potential of salidroside on CYP1A2, CYP2B6 and CYP3A4 in cryopreserved human hepatocytes, the inhibitory potential of salidroside against recombinant human MAO-A and MAO-B, and the OATP human uptake transport inhibitory potential of salidroside using transfected HEK293-OATP1B1 and OATP1B3 cells.

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COVID-19 has impacted billions of people since 2019 and unfolded a major healthcare crisis. With an increasing number of deaths and the emergence of more transmissible variants, it is crucial to better understand the biology of the disease-causing virus, the SARS-CoV-2. Peripheral neuropathies appeared as a specific COVID-19 symptom occurring at later stages of the disease.

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Regulatory T cells (Tregs) modulate tissue homeostatic processes and immune responses. Understanding tissue-Treg biology will contribute to developing precision-targeting treatment strategies. Here, we show that Tregs maintain the tolerogenic state of the testis and epididymis, where sperm are produced and mature.

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The microenvironment dictates glycocalyx construction and immune surveillance.

Res Sq

August 2023

Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco, San Francisco, CA 94143, USA.

Efforts to identify anti-cancer therapeutics and understand tumor-immune interactions are built with models that do not match the microenvironmental characteristics of human tissues. Using models which mimic the physical properties of healthy or cancerous tissues and a physiologically relevant culture medium, we demonstrate that the chemical and physical properties of the microenvironment regulate the composition and topology of the glycocalyx. Remarkably, we find that cancer and age-related changes in the physical properties of the microenvironment are sufficient to adjust immune surveillance via the topology of the glycocalyx, a previously unknown phenomenon observable only with a physiologically relevant culture medium.

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High-quality genome assemblies across a range of non-traditional model organisms can accelerate the discovery of novel aspects of genome evolution. The group has several attributes that distinguish it from more highly studied species in the genus, such as an unusual abundance of repetitive elements and extensive karyotype evolution, in addition to being an attractive model for speciation genetics. Here we used long-read sequencing to assemble five genomes of three virilis group species and characterized sequence and structural divergence and repetitive DNA evolution.

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  • Mitochondrial outer membrane α-helical proteins are essential for communication between mitochondria and the cytoplasm, but how they're targeted and inserted remains unclear.
  • A study used genome-wide CRISPRi screens to identify necessary mammalian biogenesis factors, revealing that different membrane proteins follow unique targeting pathways based on their structure.
  • Key findings include the role of NAC in targeting polytopic proteins and TTC1, a new chaperone, for signal-anchored proteins, highlighting a similar process to how proteins are managed in the endoplasmic reticulum.
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Background: Social determinants of health (SDoH), such as financial resources and housing stability, account for between 30-55% of people's health outcomes. While many studies have identified strong associations among specific SDoH and health outcomes, most people experience multiple SDoH that impact their daily lives. Analysis of this complexity requires the integration of personal, clinical, social, and environmental information from a large cohort of individuals that have been traditionally underrepresented in research, which is only recently being made available through the research program.

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Development of a Patient-Derived 3D Immuno-Oncology Platform to Potentiate Immunotherapy Responses in Ascites-Derived Circulating Tumor Cells.

Cancers (Basel)

August 2023

Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Article Synopsis
  • * Traditional immune checkpoint blockade (ICB) therapies targeting the PD-(L)1 axis have been largely ineffective, prompting researchers to explore the use of epigenetic modulators for better personalized immunotherapy outcomes.
  • * A novel 3D screening platform using patient-derived tumor samples has shown that responses to chemotherapy and immunotherapy correlate with immune cell activity and tumor characteristics, suggesting that combining epigenetic priming with ICB could enhance immune response and offer more effective treatment strategies.
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Bibliometric analysis of evolutionary trends and hotspots of super-enhancers in cancer.

Front Pharmacol

July 2023

Department of Pharmacy, The Second Xiangya Hospital, Institute of Clinical Pharmacy, Central South University, Changsha, China.

In the past decade, super-enhancer (SE) has become a research hotspot with increasing attention on cancer occurrence, development, and prognosis. To illustrate the hotspots of SE in cancer research and its evolutionary tendency, bibliometric analysis was carried out for this topic. Literature published before Dec 31, 2022, in WOSCC, was systematically classified, and Citespace, bibliometric.

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Porous tissue-engineered 3D-printed scaffolds are a compelling alternative to autografts for the treatment of large periorbital bone defects. Matching the defect-specific geometry has long been considered an optimal strategy to restore pre-injury anatomy. However, studies in large animal models have revealed that biomaterial-induced bone formation largely occurs around the scaffold periphery.

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Asymmetric Stem Cell Division and Germline Immortality.

Annu Rev Genet

November 2023

Whitehead Institute for Biomedical Research, Howard Hughes Medical Institute, and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; email:

Germ cells are the only cell type that is capable of transmitting genetic information to the next generation, which has enabled the continuation of multicellular life for the last 1.5 billion years. Surprisingly little is known about the mechanisms supporting the germline's remarkable ability to continue in this eternal cycle, termed germline immortality.

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MicroRNAs (miRNAs) pair to sites in mRNAs to direct the degradation of these RNA transcripts. Conversely, certain RNA transcripts can direct the degradation of particular miRNAs. This target-directed miRNA degradation (TDMD) requires the ZSWIM8 E3 ubiquitin ligase.

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-methyladenosine (m6A), the most abundant mRNA modification, is deposited in mammals/insects/plants by m6A methyltransferase complexes (MTC) comprising a catalytic subunit and at least five additional proteins. The yeast MTC is critical for meiosis and was known to comprise three proteins, of which two were conserved. We uncover three novel MTC components (Kar4/Ygl036w-Vir1/Dyn2).

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Cancer-associated mesothelial cells are regulated by the anti-Müllerian hormone axis.

Cell Rep

July 2023

Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA, USA; Department of Surgery, Harvard Medical School, Boston, MA, USA; Mouse Genome Informatics, The Jackson Laboratory, Bar Harbor, ME, USA. Electronic address:

Cancer-associated mesothelial cells (CAMCs) in the tumor microenvironment are thought to promote growth and immune evasion. We find that, in mouse and human ovarian tumors, cancer cells express anti-Müllerian hormone (AMH) while CAMCs express its receptor AMHR2, suggesting a paracrine axis. Factors secreted by cancer cells induce AMHR2 expression during their reprogramming into CAMCs in mouse and human in vitro models.

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