6,666 results match your criteria: "Massachusetts 02142; email: joelh@broadinstitute.org.[Affiliation]"

Dust accumulation on solar panels is a mjor operational challenge faced by the photovoltaic industry. Removing dust using water-based cleaning is expensive and unsustainable. Dust repulsion via charge induction is an efficient way to clean solar panels and recover power output without consuming any water.

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The Planetary Health Diet (PHD), also known as the EAT-Lancet reference diet, was developed to optimize global dietary quality while keeping the environmental impacts of food production within sustainable planetary boundaries. We calculated current national and global adherence to the PHD using the Planetary Health Dietary Index (PHDI). In addition, we used data on diet and mortality from three large US cohorts (n = 206,404 men and women, 54,536 deaths) to estimate the total and cause-specific mortality among adults 20 y of age and older that could be prevented by shifting from current diets to the reference PHD.

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Proteolethargy is a pathogenic mechanism in chronic disease.

Cell

January 2025

Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address:

The pathogenic mechanisms of many diseases are well understood at the molecular level, but there are prevalent syndromes associated with pathogenic signaling, such as diabetes and chronic inflammation, where our understanding is more limited. Here, we report that pathogenic signaling suppresses the mobility of a spectrum of proteins that play essential roles in cellular functions known to be dysregulated in these chronic diseases. The reduced protein mobility, which we call proteolethargy, was linked to cysteine residues in the affected proteins and signaling-related increases in excess reactive oxygen species.

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Mapping rare protein-coding variants on multi-organ imaging traits.

medRxiv

November 2024

Graduate Group in Applied Mathematics and Computational Science, University of Pennsylvania, Philadelphia, PA 19104, USA.

Human organ structure and function are important endophenotypes for clinical outcomes. Genome-wide association studies (GWAS) have identified numerous common variants associated with phenotypes derived from magnetic resonance imaging (MRI) of the brain and body. However, the role of rare protein-coding variations affecting organ size and function is largely unknown.

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PrP lowering is effective against prion disease in animal models and is being tested clinically. Therapies in the current pipeline lower PrP production, leaving pre-existing PrP to be cleared according to its own half-life. We hypothesized that PrP's half-life may be a rate-limiting factor for the time to effect of PrP-lowering drugs, and one reason why late treatment of prion-infected mice is not as effective as early treatment.

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Astrocytes, which are increasingly recognized as pivotal constituents of brain circuits governing a wide range of functions, express GABA transporter 3 (Gat3), an astrocyte-specific GABA transporter responsible for maintenance of extra-synaptic GABA levels. Here, we examined the functional role of Gat3 in astrocyte-mediated modulation of neuronal activity and information encoding. First, we developed a multiplexed CRISPR construct applicable for effective genetic ablation of Gat3 in the visual cortex of adult mice.

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Macrophages are critical effectors of antibody therapies for lymphoma, but the best targets for this purpose remain unknown. Here, we sought to define a comprehensive repertoire of cell surface antigens that can be targeted to stimulate macrophage-mediated destruction of B-cell lymphoma. We developed a high-throughput assay to screen hundreds of antibodies for their ability to provoke macrophages to attack B-cell lymphoma cells.

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Spinal motor neuron (MN) dysfunction is the cause of a number of clinically significant movement disorders. Despite the recent approval of gene therapeutics targeting these MN-related disorders, there are no viral delivery mechanisms that achieve MN-restricted transgene expression. In this study, chromatin accessibility profiling of genetically defined mouse MNs was used to identify candidate cis-regulatory elements (CREs) capable of driving MN-selective gene expression.

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Lethal COVID-19 outcomes are attributed to classic cytokine storm. We revisit this using RNA sequencing of nasopharyngeal and 40 autopsy samples from patients dying of SARS-CoV-2. Subsets of the 100 top-upregulated genes in nasal swabs are upregulated in the heart, lung, kidney, and liver, but not mediastinal lymph nodes.

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is a ubiquitous protozoan parasite that can reside long-term within hosts as intracellular tissue cysts comprised of chronic stage bradyzoites. To perturb chronic infection requires a better understanding of the cellular processes that mediate parasite persistence. Macroautophagy/autophagy is a catabolic and homeostatic pathway that is required for chronic infection, although the molecular details of this process remain poorly understood.

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Infection by retroviruses and the mobilization of transposable elements cause DNA damage that can be catastrophic for a cell. If the cell survives, the mutations generated by retrotransposition may confer a selective advantage, although, more commonly, the effect of new integrants is neutral or detrimental. If retrotransposition occurs in gametes or in the early embryo, it introduces genetic modifications that can be transmitted to the progeny and may become fixed in the germline of that species.

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Unsupervised Canine Emotion Recognition Using Momentum Contrast.

Sensors (Basel)

November 2024

MIT System Design and Management, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02142, USA.

We describe a system for identifying dog emotions based on dogs' facial expressions and body posture. Towards that goal, we built a dataset with 2184 images of ten popular dog breeds, grouped into seven similarly sized primal mammalian emotion categories defined by neuroscientist and psychobiologist Jaak Panksepp as 'Exploring', 'Sadness', 'Playing', 'Rage', 'Fear', 'Affectionate' and 'Lust'. We modified the contrastive learning framework MoCo (Momentum Contrast for Unsupervised Visual Representation Learning) to train it on our original dataset and achieved an accuracy of 43.

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Glycoconjugate vaccines: platforms and adjuvants for directed immunity.

Glycobiology

September 2024

Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, United States.

Central to immune recognition is the glycocalyx, a glycan-rich coat on all cells that plays a crucial role in interactions that enable pathogen detection and activation of immune defenses. Pathogens and cancerous cells often display distinct glycans on their surfaces, making these saccharide antigens prime targets for vaccine development. However, carbohydrates alone generally serve as poor immunogens due to their often weak binding affinities, inability to effectively recruit T cell help, and reliance on adjuvants to iboost immune activation.

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Article Synopsis
  • * A study identified a strong link between Native American ancestry and an increased risk of MeN, while certain genetic variants were found to significantly reduce the odds of developing the disease.
  • * Findings suggest that genetic differences in sensitivity to heat and dehydration contribute to the prevalence of kidney disease in these workers, highlighting both environmental and genetic factors.
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Cities exhibit consistent returns to scale in economic outputs, and urban scaling analysis is widely adopted to uncover common mechanisms in cities' socioeconomic productivity. Leading theories view cities as closed systems, with returns to scale arising from intra-city social interactions. Here, we argue that the interactions between cities, particularly via shared organizations such as firms, significantly influence a city's economic output.

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Resistance to immunomodulatory drugs in multiple myeloma: the cereblon pathway and beyond.

Haematologica

November 2024

Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore; Division of Haematology, Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), National University Health System, 119228.

Acquired resistance to immunomodulatory drugs (IMiDs) remains a significant unmet need in the treatment landscape of multiple myeloma (MM). CRBN pathway-dependent mechanisms are known to be vital contributors to IMiD resistance; however, they may account for only a small proportion. Recent research has unveiled additional mechanisms of acquired IMiD resistance that are independent of the CRBN pathway.

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Manual review is an integral part of any study. As the cost of data generation continues to decrease, the rapid rise in large-scale multi-omic studies calls for a modular, flexible framework to perform what is currently a tedious, error-prone process. We developed , a Python-based package built with Plotly Dash that creates interactive, highly customizable dashboards for reviewing and annotating data.

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GENCODE 2025: reference gene annotation for human and mouse.

Nucleic Acids Res

January 2025

European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.

GENCODE produces comprehensive reference gene annotation for human and mouse. Entering its twentieth year, the project remains highly active as new technologies and methodologies allow us to catalog the genome at ever-increasing granularity. In particular, long-read transcriptome sequencing enables us to identify large numbers of missing transcripts and to substantially improve existing models, and our long non-coding RNA catalogs have undergone a dramatic expansion and reconfiguration as a result.

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Content moderators review problematic content for technology companies. One concern is that repeated exposure to false claims could cause moderators to come to believe the very claims they are supposed to moderate, via the "illusory truth effect." In a first lab-in-field experiment ( = 199) with a global content moderation company, we found that exposure to false claims while working as moderators increased subsequent belief among (mostly Indian and Philippine) employees by 7.

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In vivo photoreceptor base editing ameliorates rhodopsin-E150K autosomal-recessive retinitis pigmentosa in mice.

Proc Natl Acad Sci U S A

November 2024

Gavin Herbert Eye Institute-Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA 92617.

Rhodopsin, the prototypical class-A G-protein coupled receptor, is a highly sensitive receptor for light that enables phototransduction in rod photoreceptors. Rhodopsin plays not only a sensory role but also a structural role as a major component of the rod outer segment disc, comprising over 90% of the protein content of the disc membrane. Mutations in which lead to structural or functional abnormalities, including the autosomal recessive E150K mutation, result in rod dysfunction and death.

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Article Synopsis
  • - Accurate gene annotations are essential for interpreting how genomes function, and the GENCODE consortium has spent twenty years creating reference annotations for human and mouse genomes, serving as a vital resource for researchers globally.
  • - Previous annotations of long non-coding RNAs (lncRNAs) were incomplete and poorly organized, hindering research, prompting GENCODE to launch a comprehensive effort that resulted in adding nearly 18,000 novel human genes and over 22,000 novel mouse genes, significantly increasing the catalog of transcripts.
  • - The new annotations not only show evolutionary patterns and link to genetic variants associated with traits but also improve understanding of previously unclear genomic functions, greatly advancing research into both human and mouse genetic diseases.
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Understanding how human gene expression is coordinately regulated by functional units of proteins across the genome remains a major biological goal. Here, we present COMET, a high-throughput screening platform for combinatorial effector targeting for the identification of transcriptional modulators. We generate libraries of combinatorial dCas9-based fusion proteins, containing two to six effector domains, allowing us to systematically investigate more than 110,000 combinations of effector proteins at endogenous human loci for their influence on transcription.

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Analysis of multi-modal datasets can identify multi-scale interactions underlying biological systems, but can be beset by spurious connections due to indirect impacts propagating through an unmapped biological network. For example, studies in macaques have shown that BCG vaccination by an intravenous route protects against tuberculosis, correlating with changes across various immune data modes. To eliminate spurious correlations and identify critical immune interactions in a public multi-modal dataset (systems serology, cytokines, cytometry) of vaccinated macaques, we applied Markov Fields (MF), a data-driven approach that explains vaccine efficacy and immune correlations via multivariate network paths, without requiring large numbers of samples (i.

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Chemical proteomics enables the global analysis of small molecule-protein interactions in native biological systems and has emerged as a versatile approach for ligand discovery. The range of small molecules explored by chemical proteomics has, however, remained limited. Here, we describe a diversity-oriented synthesis (DOS)-inspired library of stereochemically defined compounds bearing diazirine and alkyne units for UV light-induced covalent modification and click chemistry enrichment of interacting proteins, respectively.

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A closed-loop modular multiorgan-on-chips platform for self-sustaining and tightly controlled oxygenation.

Proc Natl Acad Sci U S A

November 2024

Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139.

To mimic physiological microenvironments in organ-on-a-chip systems, physiologically relevant parameters are required to precisely access drug metabolism. Oxygen level is a critical microenvironmental parameter to maintain cellular or tissue functions and modulate their behaviors. Current organ-on-a-chip setups are oftentimes subjected to the ambient incubator oxygen level at 21%, which is higher than most if not all physiological oxygen concentrations.

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