Publications by authors named "King I"

Genome editing using CRISPR-Cas systems is a promising avenue for the treatment of genetic diseases. However, cellular and humoral immunogenicity of genome editing tools, which originate from bacteria, complicates their clinical use. Here we report reduced immunogenicity (Red)(i)-variants of two clinically relevant nucleases, SaCas9 and AsCas12a.

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The gut mycobiota is crucial for intestinal homeostasis and immune function. Yet its variability and inconsistent fungal colonization of laboratory mice hinders the study of the evolutionary and immune processes that underpin commensalism. Here, we show that Kazachstania pintolopesii is a fungal commensal in wild urban and rural mice, with an exceptional ability to colonize the mouse gastrointestinal tract and dominate the gut mycobiome.

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Accurate prediction of RNA three-dimensional (3D) structures remains an unsolved challenge. Determining RNA 3D structures is crucial for understanding their functions and informing RNA-targeting drug development and synthetic biology design. The structural flexibility of RNA, which leads to the scarcity of experimentally determined data, complicates computational prediction efforts.

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RNAs represent a class of programmable biomolecules capable of performing diverse biological functions. Recent studies have developed accurate RNA three-dimensional structure prediction methods, which may enable new RNAs to be designed in a structure-guided manner. Here, we develop a structure-to-sequence deep learning platform for the de novo generative design of RNA aptamers.

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Article Synopsis
  • Bioinformatics is experiencing significant advancements through the use of foundation models (FMs) in AI, which help address challenges like limited annotated data and data noise, marking a crucial shift in computational biology.
  • The survey aims to summarize the evolution, current research landscape, and methodologies of FMs in bioinformatics, with a focus on their applications to specific biological problems such as sequence analysis and structure prediction.
  • The review discusses challenges faced by FMs, such as data noise and interpretability, while providing insights and potential directions for future developments in the application of FMs within biological research.
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  • - Paneth cells in the intestinal crypts help support stem cells and immunity by producing growth factors and antimicrobial peptides.
  • - A study by Wallaeys et al. discusses how these Paneth cells respond to TNF (tumor necrosis factor), which affects their ability to manage stress in proteins.
  • - This disruption leads to a decrease in antimicrobial peptides, increasing the risk of bacteria moving into the bloodstream and potentially causing sepsis.
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In the lower respiratory tract, the alveolar spaces are divided from the bloodstream and the external environment by only a few microns of interstitial tissue. Alveolar macrophages (AMs) defend this delicate mucosal surface from invading infections by regularly patrolling the site. AMs have three behavior modalities to achieve this goal: extending cell protrusions to probe and sample surrounding areas, squeezing the whole cell body between alveoli, and patrolling by moving the cell body around each alveolus.

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  • The British Orthopaedic Association Standards for Trauma and Orthopaedics (BOAST) provide guidelines for treating open lower limb fractures, and an audit was conducted to evaluate the adherence to these standards in a Southeast England trauma center.
  • The audit analyzed data from 133 patients from August 2020 to August 2022, revealing that most patients were older women who sustained fractures from low-energy injuries, with a significant number undergoing timely debridement and closure procedures.
  • While the management of these fractures generally aligned with BOAST guidelines, improvements are needed in initial debridement practices, emphasizing the importance of training and resource allocation to enhance compliance.
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  • Reliable pQCT assessment is crucial for accurately tracking changes in bone and muscle quality over time, but its reliability across different days and age groups hasn't been fully explored.
  • *The study involved 72-86 participants (both men and women) aged 18-85, who completed two days of pQCT testing to measure the accuracy of bone, muscle area, and fat metrics.
  • *Most measurements showed good to excellent reliability, but muscle density showed poorer reliability in certain areas, with older adults experiencing increased biological error, particularly in forearm muscle density.
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Inflammatory bowel diseases (IBD) are chronic inflammatory diseases in which abdominal pain, bloody diarrhea, weight loss, and fatigue collectively result in diminished quality of patient life. The disappearance of intestinal helminth infections in Western societies is associated with an increased prevalence of IBD and other immune-mediated inflammatory diseases. Evidence indicates that helminths induce tolerogenic dendritic cells (tolDCs), which promote intestinal tolerance and attenuate intestinal inflammation characteristic of IBD, but the exact mechanism is unclear.

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The use of plant genetic resources (PGR)-wild relatives, landraces, and isolated breeding gene pools-has had substantial impacts on wheat breeding for resistance to biotic and abiotic stresses, while increasing nutritional value, end-use quality, and grain yield. In the Global South, post-Green Revolution genetic yield gains are generally achieved with minimal additional inputs. As a result, production has increased, and millions of hectares of natural ecosystems have been spared.

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Time series are the primary data type used to record dynamic system measurements and generated in great volume by both physical sensors and online processes (virtual sensors). Time series analytics is therefore crucial to unlocking the wealth of information implicit in available data. With the recent advancements in graph neural networks (GNNs), there has been a surge in GNN-based approaches for time series analysis.

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The identification of protein homologs in large databases using conventional methods, such as protein sequence comparison, often misses remote homologs. Here, we offer an ultrafast, highly sensitive method, dense homolog retriever (DHR), for detecting homologs on the basis of a protein language model and dense retrieval techniques. Its dual-encoder architecture generates different embeddings for the same protein sequence and easily locates homologs by comparing these representations.

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The ubiquitous soil-associated fungus causes pneumonia that may progress to fatal meningitis. Recognition of fungal cell walls by C-type lectin receptors (CLRs) has been shown to trigger the host immune response. Caspase recruitment domain-containing protein 9 (Card9) is an intracellular adaptor that is downstream of several CLRs.

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Background: A growing body of research indicates that associations of ceramides and sphingomyelins with mortality depend on the chain length of the fatty acid acylated to the backbone sphingoid base. We examined associations of 8 ceramide and sphingomyelin species with mortality among an American Indian population.

Methods And Results: The analysis comprised 2688 participants from the SHFS (Strong Heart Family Study).

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CRTC1::TRIM11 cutaneous tumor (CTCT) is a rare skin tumor of uncertain differentiation. In the 49 reported cases, only four cases showed regional or distant metastasis, but follow-up remains limited. Herein, we present a case of metastatic CTCT with ulceration, a histological feature that has not been previously described.

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Article Synopsis
  • - The study investigates the genetic factors contributing to chronic post-surgical pain (CPSP) by analyzing data from 1,350 individuals who underwent various types of surgery, and highlights a significant genetic component, estimating a 39% heritability for CPSP through meta-analysis.
  • - Researchers identified 77 key genetic variations (SNPs) linked to CPSP and noted that most of these are associated with immune system genes, especially those related to B and T cells.
  • - Animal studies showed that mice without T and B cells experienced worsened pain after surgery, which could be mitigated by transferring B cells, suggesting that the adaptive immune system plays a crucial protective role against CPSP.
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There is rapidly growing awareness of microbiome assembly and function in early-life gut health. Although many factors, such as antibiotic use and highly processed diets, impinge on this process, most research has focused on people residing in high-income countries. However, much of the world's population lives in low- and middle-income countries (LMICs), where, in addition to erratic antibiotic use and suboptimal diets, these groups experience unique challenges.

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Wheat (Triticum aestivum) is one of the most important food crops with an urgent need for increase in its production to feed the growing world. Triticum timopheevii (2n = 4x = 28) is an allotetraploid wheat wild relative species containing the A and G genomes that has been exploited in many pre-breeding programmes for wheat improvement. In this study, we report the generation of a chromosome-scale reference genome assembly of T.

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Background: Elexacaftor/tezacaftor/ivacaftor (ETI) has revolutionized cystic fibrosis (CF) treatment. However, previous research has demonstrated profound global disparities in diagnosis and treatment access. If unaddressed, these threaten to widen existing health inequities.

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Single-cell RNA sequencing has achieved massive success in biological research fields. Discovering novel cell types from single-cell transcriptomics has been demonstrated to be essential in the field of biomedicine, yet is time-consuming and needs prior knowledge. With the unprecedented boom in cell atlases, auto-annotation tools have become more prevalent due to their speed, accuracy and user-friendly features.

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Background: Excessive or inappropriate use of social media has been linked to disruptions in regular work, well-being, mental health, and overall reduction of quality of life. However, a limited number of studies documenting the impact of social media on health-related quality of life (HRQoL) are available globally.

Aim: This study aimed to explore the perceived social media needs and their impact on the quality of life among the adult population of various selected countries.

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Maintenance of CD4 T cells during chronic infections is vital for limiting pathogen burden and disease recrudescence. Although inhibitory receptor expression by CD4 T cells is commonly associated with immune suppression and exhaustion, such cell-intrinsic mechanisms that control activation are also associated with cell survival. Using a mouse model of visceral leishmaniasis (VL), we discovered a subset of lymphocyte activation gene 3 (LAG-3)-expressing CD4 T cells that co-express CXCR5.

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Patients diagnosed with localized high-risk prostate cancer have higher rates of recurrence, and the introduction of neoadjuvant intensive hormonal therapies seeks to treat occult micrometastatic disease by their addition to definitive treatment. Sufficient profiling of baseline disease has remained a challenge in enabling the in-depth assessment of phenotypes associated with exceptional vs. poor pathologic responses after treatment.

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