15,579 results match your criteria: "a Institute of Biochemistry and Biophysics; Polish Academy of Sciences ; Warsaw[Affiliation]"

The IsletTester mouse: an immunodeficient model with stable hyperglycemia for the study of human islets.

Diabetes

November 2024

Institute of Diabetes, Obesity, and Metabolism, Perelman School of Medicine, The University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA, USA 19104.

Article Synopsis
  • The current gold standard for testing human islet or stem cell-derived β-like cell function involves implanting them in immunodeficient mice, but existing models have limitations like unstable hyperglycemia and high morbidity.
  • Researchers developed the IsletTester mouse using CRISPR-Cas9 to create a stable hyperglycemic model, showing normal life span and fertility with consistent glucose levels.
  • This new model allows for better study of human islet biology and serves as a valuable preclinical tool for evaluating stem cell-derived islet products.
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Whole-brain spatial transcriptional analysis at cellular resolution.

Science

November 2024

Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Article Synopsis
  • * The researchers developed a new method called TRISCO, which helps retain RNA signals in cleared organs for better imaging, specifically for whole-brain 3D RNA visualization.
  • * TRISCO effectively preserves RNA integrity, ensures uniform labeling, and enhances tissue transparency, making it a powerful tool for detailed transcriptional spatial analysis at the single-cell level across various organs.
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We performed whole-genome sequencing of LU150, a human fecal isolate from the NORDBIOTIC collection. The genome consists of 2,039,406 bp with a GC content of 38.9%.

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Computational analyses of transcriptomic data have dramatically improved our understanding of complex diseases. However, such approaches are limited by small sample sets of disease-affected material. We asked if a variational autoencoder trained on large groups of healthy human RNA sequencing (RNA-seq) data can capture the fundamental gene regulation system and generalize to unseen disease changes.

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The prebiotic formation of RNA building blocks is well-supported experimentally, yet the emergence of sequence- and structure-specific RNA oligomers is generally attributed to biological selection via Darwinian evolution rather than prebiotic chemical selectivity. In this study, we used deep sequencing to investigate the partitioning of randomized RNA overhangs into ligated products by either splinted ligation or loop-closing ligation. Comprehensive sequence-reactivity profiles revealed that loop-closing ligation preferentially yields hairpin structures with loop sequences UNNG, CNNG, and GNNA (where N represents A, C, G, or U) under competing conditions.

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Liver X receptor unlinks intestinal regeneration and tumorigenesis.

Nature

November 2024

Division of Immunology and Respiratory Medicine, Department of Medicine Solna, Karolinska Institutet and University Hospital, Stockholm, Sweden.

Article Synopsis
  • Uncontrolled regeneration in the intestinal epithelium can lead to cancer, highlighting the need for precise regulation during tissue renewal.
  • Researchers discovered that activating the liver X receptor (LXR) pathway helps balance intestinal regeneration and tumor growth after damage.
  • LXR activation enhances regeneration by producing amphiregulin and is crucial for controlling tumor growth, with diminished LXR-related activity found in human colorectal cancer samples.
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The proteome integral solubility alteration (PISA) assay is widely used for identifying drug targets, but it is labor-intensive and time-consuming and requires a substantial amount of biological sample. Aiming at enabling automation and greatly reducing the sample amount, we developed one-pot time-induced (OPTI)-PISA. Here, we demonstrate OPTI-PISA performance on identifying targets of multiple drugs in cell lysate and scaling down the sample amount to sub-microgram levels, making the PISA method suitable for NanoProteomics.

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The overexpression and misfolding of viral proteins in the endoplasmic reticulum (ER) may cause cellular stress, thereby inducing a cytoprotective, proteostatic host response involving phosphorylation of eukaryotic translation initiation factor 2 subunit alpha (eIF2α). Here, we show that hepatitis A virus, a positive-strand RNA virus responsible for infectious hepatitis, adopts a stress-resistant, eIF2α-independent mechanism of translation to ensure the synthesis of viral proteins within the infected liver. Cap-independent translation directed by the hepatovirus internal ribosome entry site and productive hepatovirus infection of mice both require platelet-derived growth factor subunit A (PDGFA)-associated protein 1 (PDAP1), a small phosphoprotein of unknown function with eIF4E-binding activity.

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Article Synopsis
  • Secretory proteins rely on the signal peptidase complex (SPC) for proper processing of their signal sequences, which is vital for correct protein folding and placement in eukaryotic cells.
  • The study focused on the role of Spc2 within the SPC, showing that mutations or depletion of Spc2 hinder the complex’s ability to recognize and cleave substrates correctly.
  • Molecular dynamics simulations revealed that without Spc2, the SPC's membrane structure is altered, shedding light on how Spc2 affects the protein biogenesis process.
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GABA Receptors and K7 Channels as Targets for GABAergic Regulation of Acetylcholine Release in Frog Neuromuscular Junction.

Neurochem Res

November 2024

Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, 2/31 Lobachevsky St, Kazan, 420111, Russia.

Article Synopsis
  • The study investigated the effects of gamma-aminobutyric acid (GABA) and selective GABAergic ligands on acetylcholine (ACh) release at frog neuromuscular junctions using microelectrode techniques alongside fluorescent and immunohistochemical assays.
  • It was found that GABA significantly reduced ACh release; however, this effect wasn't completely reversed by GABA antagonists, indicating a complex interaction.
  • Additionally, GABA was shown to activate specific K7 potassium channels directly, suggesting that endogenous GABA may play a role in regulating neurotransmitter release during muscle contraction.
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Sustained immune activation and impaired epithelial barrier integrity in the ectocervix of women with chronic HIV infection.

PLoS Pathog

November 2024

Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, Sweden.

Chronic systemic immune activation significantly influences human immunodeficiency virus (HIV) disease progression. Despite evidence of a pro-inflammatory environment in the genital tract of HIV-infected women, comprehensive investigations into cervical tissue from this region remain limited. Similarly, the consequences of chronic HIV infection on the integrity of the female genital epithelium are poorly understood, despite its importance in HIV transmission and replication.

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Optimized and Robust Workflow for Quantifying the Canonical Histone Ubiquitination Marks H2AK119ub and H2BK120ub by LC-MS/MS.

J Proteome Res

December 2024

Penn Epigenetics Institute, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.

Article Synopsis
  • The eukaryotic genome is organized with histone proteins that undergo various post-translational modifications, which play a crucial role in epigenetic regulation by controlling DNA accessibility.
  • Mass spectrometry is a key technique for studying these modifications, particularly for analyzing histone N-terminal tails, but methods for examining ubiquitin marks on histone C-terminal regions are less developed.
  • The authors present a new, simple workflow to detect and quantify specific histone ubiquitination marks (H2AK119ub and H2BK120ub) through a streamlined process that enhances existing methods focused on N-terminal modifications.
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Liquid-liquid phase condensation governs a wide range of protein-protein and protein-RNA interactions in vivo and drives the formation of membrane-less compartments such as the nucleolus and stress granules. We have a broad overview of the importance of multivalency and protein disorder in driving liquid-liquid phase transitions. However, the large and complex nature of key proteins and RNA components involved in forming condensates such as stress granules has inhibited a detailed understanding of how condensates form and the structural interactions that take place within them.

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Embryos undergo pre-gastrulation cleavage cycles to generate a critical cell mass before transitioning to morphogenesis. The molecular underpinnings of this transition have traditionally centered on zygotic chromatin remodeling and genome activation, as their repression can prevent downstream processes of differentiation and organogenesis. Despite precedents that oxygen depletion can similarly suspend development in early embryos, hinting at a pivotal role for oxygen metabolism in this transition, whether there is a chemical switch that licenses the onset of morphogenesis remains unknown.

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Human serum albumin (HSA), a crucial plasma protein, plays a significant role in drug interactions within the bloodstream, bearing considerable clinical relevance. Bortezomib (BTZ) is a potent anti-cancer drug for multiple myeloma (MM) and mantle cell lymphoma (MC). The mechanism of BTZ transfer in the blood remains undetermined.

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Yaghooti grape, as the earliest grape variety in Iran, is considered as more resistant to heat, drought, and salinity than other cultivars. Cluster compactness is regarded as an inappropriate feature for the productivity of Yaghooti grape as a critical commercial and nutritional product. In plants, lncRNAs play a critical role in regulating biological processes related to growth and development.

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Fragile X messenger ribonucleoprotein (FMRP) is a critical regulator of translation, whose dysfunction causes fragile X syndrome. FMRP dysfunction disrupts mitochondrial health in neurons, but it is unclear how FMRP supports mitochondrial homoeostasis. Here we demonstrate that FMRP granules are recruited to the mitochondrial midzone, where they mark mitochondrial fission sites in axons and dendrites.

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Psychotropic-induced weight gain and telomere length: results from a one-year longitudinal study and a large population-based cohort.

Transl Psychiatry

November 2024

Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Lausanne, Prilly, Switzerland.

Weight-inducing psychotropic treatments are risk factors for age-related diseases such as cardiovascular disorders, which are associated with both inflammation and telomere length shortening. With a longitudinal design, the present study evaluates telomere length trajectories after 1 year of weight-inducing psychotropic medication, accounting for weight changes and the inflammatory biomarker high-sensitivity C-Reactive Protein (CRP). Among 200 patients, an overall median telomere shortening of -41.

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Serum proteomics identifies biomarkers for predicting non-survivors in elderly COVID-19 patients.

J Proteomics

January 2025

Center for Precision Medicine Multi-Omics Research, Institute of Advanced Clinical Medicine, Peking University, Beijing 100191, China; Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address:

In December 2022, China ceased the zero-COVID-19 policy, resulting in an increase in hospitalizations and deaths due to COVID-19, particularly among the elderly population. Predicting non-survivors aims to identify high-risk patients and enable targeted interventions to improve survival rates. Additionally, understanding factors affecting prognosis provides essential insights for further research and optimization of treatment strategies.

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Discovery and significance of protein-protein interactions in health and disease.

Cell

November 2024

Quantitative Biosciences Institute, University of California, San Francisco (UCSF), San Francisco, CA, USA; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco (UCSF), San Francisco, CA, USA. Electronic address:

The identification of individual protein-protein interactions (PPIs) began more than 40 years ago, using protein affinity chromatography and antibody co-immunoprecipitation. As new technologies emerged, analysis of PPIs increased to a genome-wide scale with the introduction of intracellular tagging methods, affinity purification (AP) followed by mass spectrometry (MS), and co-fractionation MS (CF-MS). Now, combining the resulting catalogs of interactions with complementary methods, including crosslinking MS (XL-MS) and cryogenic electron microscopy (cryo-EM), helps distinguish direct interactions from indirect ones within the same or between different protein complexes.

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β-Ionone is the end-ring counterpart of β-carotenoids, which are widely found in fruits and vegetables. Recent studies have illustrated the antimetastatic, anti-proliferative, and apoptosis-inducing activities of β-ionone both in vitro and in vivo. We aimed to explore the anti-cancer potency of β-Ionone-derived ester, (E)-4-(2,6,6-trimethylcyclohex-1-enyl) but-3-en-2-ylpyrazine-2-carboxylate (4-TM.

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Systematic screens for fertility genes essential for malaria parasite transmission reveal conserved aspects of sex in a divergent eukaryote.

Cell Syst

November 2024

The Laboratory for Molecular Infection Medicine Sweden, Umeå University, Umeå, Sweden; Department of Molecular Biology, Umeå University, Umeå, Sweden. Electronic address:

Article Synopsis
  • Sexual reproduction in malaria parasites is crucial for their transmission to mosquitoes and helps researchers explore the evolution of sexual reproduction across different eukaryotes.
  • A genetic study of Plasmodium berghei has identified 348 genes involved in sex and transmission, revealing new targets for potential interventions to block transmission.
  • The study highlights the importance of two proteins, SUN1 and ALLC1, in male fertility by connecting cellular structures necessary for sperm development, suggesting a long-standing role for these proteins across species, including in mouse testes.
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Safe and effective cancer therapy requires a suitable nanocarrier that can target particular sites, such as cancer cells, in a selective manner. With the tremendous growth in nanotechnology, liposomes, among various competing nanocarriers, have shown promising advances in cancer therapy. Magnetic nanoparticles and metal ions are wide-reaching candidates for conferring magnetic properties and for incorporation into liposomes.

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The Pfam protein families database: embracing AI/ML.

Nucleic Acids Res

January 2025

European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton CB10 1SD, UK.

The Pfam protein families database is a comprehensive collection of protein domains and families used for genome annotation and protein structure and function analysis (https://www.ebi.ac.

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