Daily Podcast 2026-03-14
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Papers & News (40)
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- [2]Protein Science, Volume 35, Issue 4, April 2026.
- [3]A variant of the U1A protein containing four substitutions to ionizable residues was generated serendipitously due to a miscommunication. Biophysical measurements show that this variant has at least twice as much helical structure as the wild-type U1A and is trimeric in solution, in contrast to the monomeric wild type. In sharp contrast, structures predic...DD
- [4]Deep learning methods for protein structure generation, sequence design, and structure and property prediction have created unprecedented opportunities for protein engineering and drug discovery. However, using these tools often requires navigating incompatible software environments, diverse input/output formats, and high-performance computing infrastruct...DD
- [5]Biomolecular functions are governed by dynamic conformational ensembles rather than static structures. While models like AlphaFold have revolutionized static structure prediction, accurately capturing the equilibrium distribution of all-atom biomolecular interactions remains a significant challenge due to the high computational cost of molecular dynamics ...DD
- [6]In recent years, the number of known protein structures has increased significantly. Predictive algorithms and experimental methods provide the positions of protein residues relative to each other with high accuracy. However, the local quality of the protein structure, including bond lengths, angles, and positions of individual atoms, often lacks the same...DD
- [7]Machine learning has driven rapid progress in protein structure prediction and design, but key challenges remain such as predicting protein structures when evolutionary information is unavailable, modeling full conformational landscapes, and capturing the thermodynamics of mutations and conformational changes. To address these problems we developed Protei...
- [8]The four major isoforms encoded by RAS proto-oncogenes are differentially associated with cancer, but there are few isoform-specific binding reagents becasue the sequence differences are confined to their disordered C termini. To overcome this limitation, we use deep learning-based methods to design Ras isoform-specific binders (RIBs) for all major Ras is...
- [9]Multidomain fusion proteins, such as bispecific antibodies, rely on highly flexible linker regions for their therapeutic efficacy. Characterizing these vast conformational ensembles is crucial for rational drug design; however, while all-atom molecular dynamics (MD) is the traditional gold standard, its immense computational cost makes simulating large-sc...
- [10]With the advent of complete genome assemblies, genome annotation has become essential for the functional interpretation of genomic data. Long-read RNA sequencing (LR-RNAseq) technologies have significantly improved transcriptome annotation by enabling full-length transcript reconstruction for both coding and non-coding RNAs. However, challenges such as tr...
- [11]The accuracy of spatial gene expression profiles generated by probe-based in situ spatially-resolved transcriptomic technologies depends on the specificity with which probes bind to their intended target gene. Off-target binding, defined as a probe binding to something other than the target gene, can distort a gene's true expression profile, making probe ...
- [12]Accurate RNA splicing is essential for gene expression and protein function, yet the mechanisms governing splice site recognition remain incompletely understood. Aberrant splicing caused by mutations can lead to severe diseases, including cancer and genetic disorders, underscoring the need for accurate computational tools to predict splice sites and detec...
- [13]Motivation: Local Ancestry Inference (LAI) allows us to study evolutionary processes in admixed populations, uncover ancestry-specific disease risk factors, and to better understand the demographic history of these populations. Many methods for LAI exist, however, these methods usually focus on cases of intercontinental admixture. In this work, we evaluat...
- [14]As a product of cellular metabolic activity, the level change of metabolites is closely related to the occurrence and development of diseases, so the prediction of metabolite-disease association is a key issue in biomedical research. Traditional methods face the challenges of insufficient long-range dependency modeling and poor interpretability. To addres...
- [15]Nature, Published online: 14 March 2026; doi:10.1038/d41586-026-00814-3 The new five-year plan calls for more original scientific research to facilitate the country's bid for self-reliance.
- [16]Microexons are short exons that are highly conserved in vertebrates and are essential for neurodevelopment. Their small size poses a challenge for regulatory protein binding and exon-definition splice site recognition, which typically relies on standard length exons. Here, we determine the sequence and RNA structural features of neural microexons in human...
- [17]Contractile injection systems (CISs) - bacteriophage tails, tailocins, and bacterial type VI secretion systems - penetrate the envelope of the target cell by employing a contractile sheath-rigid tube mechanism. The membrane-attacking end of the tube carries a spike-shaped complex that ends with a spike tip. In bacteriophage P2, the spike and spike tip pro...
- [18]Resolving the biological and geological events that led to the origin of eukaryotes is an ongoing challenge in biology. A major step in the evolution of complex cellular life was the merger between an ancestral host cell and a bacterium (that became the mitochondrion) some two billion years ago. Recently, metagenomics has enabled the reconstruction of a b...
- [19]The present study reports the metabolic profiling and antimicrobial evaluation of Vitex negundo seed extract. UHPLC-QTOF-MS/MS analysis identified seventeen bioactive phytoconstituents, correlated with the observed antimicrobial and antifungal activities. Among them, isoorientin (-7.3 kcal molββ»βΒΉ), quercetin (-7.8 kcal molββ»βΒΉ), and orientin (-7.4 kcal m...
- [20]Xylene is a common industrial solvent that includes three isomers: o-xylene, m-xylene, and p-xylene. Long-term exposure to low doses of xylene in the environment has been linked to a higher risk of lung cancer. However, the molecular mechanisms behind this link are still not fully understood. In this study, we used a combination of network toxicology and ...
- [21]Xenotransplantation offers a potential solution to the organ shortage crisis. Multi-gene modification of pigs, such as knockout of three carbohydrate antigen-related genes and expression of immunoprotective proteins, can significantly improve xenograft survival. However, existing strategies face challenges: transposon-based transgenesis may lead to unstab...
- [22]A definitive correlate of protection (CoP) for SARS-CoV-2 has yet to be formally established. Previously, using data from a series of non-human primate vaccine challenge studies, we reported that neutralising antibodies (NAbs) are the strongest candidate for clinical protection against COVID-19 and that spike binding antibody is the strongest candidate Co...
- [23]The global aging population faces heightened vulnerability to infectious diseases due to immunosenescence, which diminishes the potency, durability, and breadth of vaccine-induced immunity. While the leading shingles vaccine, Shingrix, provides protection against herpes zoster virus for adults aged 50 and older, it is often associated with severe local an...
- [24]Single-pass transmembrane proteins neuroligin (NL) and neurexin (NRX) constitute a pair of synaptic adhesion molecules that are essential for the formation of functional synapses. Binding affinities vary by ~1000-fold between combinations of NL and NRX subtypes, which contribute to chemical and spatial specificities. Among major NL-NRX subtypes, NL2 and N...
- [25]Antigen loss is a major mechanism of resistance to immunotherapy. MIC-A/B are stress-inducible ligands expressed by tumor cells that activate NKG2D on cytotoxic immune cells and mediate NKG2D-dependent tumor cell killing, yet the mechanisms underlying their reduced expression in glioma remain unclear. Using single-cell RNA sequencing and spatial transcrip...
- [26]The ability to sequence proteins without reliance on a genomic template defines a critical frontier in proteomics. This approach, known as de novo protein sequencing, is essential for applications in antibody sequencing, microbiome proteomics, and antigen discovery, which require accurate reconstruction of target sequences. To advance this field, we here ...
- [27]Traditional computational protein design heavily relies on expert-level biological inputs to define structural and functional constraints, posing significant barriers in terms of technical implementation and workflow construction. To address this gap, we capitalize on recent advancements in large language models (LLMs)βwhich excel at complex reasoning in ...
- [28]The flexibility of DNA and RNA is known to play a central role in numerous biological processes, including chromatin organization and gene regulation. While a wide range of computational approaches have been developed to investigate the conformational dynamics and flexibility of proteins, analogous methods for nucleic acids remain comparatively underexplo...
- [29]Protein Science, Volume 35, Issue 4, April 2026.
- [30]BACKGROUND: Adult-type gliomas are among the most prevalent and lethal primary central nervous system tumors, where prompt and accurate diagnosis is essential for maximizing survival prospects. Molecular classification, particularly the detection of isocitrate dehydrogenase (IDH) mutations and 1p/19q codeletions, has become crucial for accurate diagnosis ...
- [31]BACKGROUND: A large wave of COVID-19 caused by SARS-CoV-2 Omicron subvariants began in Beijing in early December 2022. OBJECTIVE: This study aimed to evaluate the COVID-19 vaccine effectiveness (VE) in mitigating the risk of COVID-19-related hospitalization during the epidemic. METHODS: We conducted a retrospective cohort study linking regional health car...
- [32]Epistasis-the context-dependence of mutational effects-is a key driver of protein evolution, influencing adaptive pathways and functional diversity. While specific epistasis arises from direct physical interactions between mutations, non-specific epistasis emerges when a non-linear mapping links a protein's biophysical properties to its function. Enzyme k...
- [33]Current SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccines have shown robust induction of neutralizing antibodies and CD4
- [34]BACKGROUND: Mixed response, where different lesions within the same patient show discordant responses to treatment, remains poorly understood. To better understand the complex effects of mixed response on patient survival, we devised three different definitions of mixed response. This retrospective analysis provides the first evaluation of the association...
- [35]Plant-pathogenic fungi cause crop disease via a range of secreted effector proteins that interact with specific receptors of host plant cells. Effector identification can enable the diagnosis of disease outcomes and enable selection or breeding of disease-resistant crop cultivars. Bioinformatic methods have been developed to predict proteins with 'effecto...
- [36]OBJECTIVES: The significant morbidity and mortalities from, and the recurrent outbreaks of, the vaccine-preventable infectious diseases (VPDs) of childhood could be due not only to non-receipt of recommended vaccinations but also to untimely receipt, which impairs the validity of immunisation coverage and protection against VPDs. This study explored the d...
- [37]Interim estimates of state-level influenza vaccine effectiveness (VE) can help guide timely local public health actions for prevention and treatment of influenza. Linked influenza vaccination and public health influenza surveillance data from California allowed estimation of interim influenza VE by comparing the odds of seasonal influenza vaccination amon...
- [38]In the United States, annual influenza vaccination has been recommended for all persons aged β₯6 months, including during the 2025-26 season. Interim influenza vaccine effectiveness (VE) estimates were calculated for patients with acute respiratory illness-associated outpatient visits and hospitalizations from three U.S. respiratory virus VE networks durin...
- [39]Cells are organized to form three-dimensional structures of complex tissues. To map the complete 3D organization of a tissue, technologies based on tissue microdissections provide deep bulk RNA sequencing of orthographically arranged cryosections of a tissue, such that the full 3D spatial structure could be inferred from deeply sequenced transcriptomes in...
- [40]arXiv:2602.19912v2 Announce Type: replace Abstract: Mass spectrometry is a powerful and widely used tool for identifying molecular structures due to its sensitivity and ability to profile complex samples. However, translating spectra into full molecular structures is a difficult, under-defined inverse problem. Overcoming this problem is crucial for enabl...