SRPK2 Mediates HBV Core Protein Phosphorylation and Capsid Assembly via Docking Interaction.

Members of the serine-arginine protein kinase (SRPK) family, SRPK1 and SRPK2, phosphorylate the hepatitis B core protein (Cp) and are crucial for pregenomic RNA encapsidation during viral nucleocapsid assembly. Among them, SRPK2 exhibits higher kinase activity toward Cp. In this study, we identified Cp sites that are phosphorylated by SRPK2 and demonstrated that the kinase utilizes an SRPK-specific docking groove to interact with and regulate the phosphorylation of the C-terminal arginine rich domain of Cp.

The beauty and complexity of the small heat shock proteins: a report on the proceedings of the fourth workshop on small heat shock proteins.

The Fourth Cell Stress Society International workshop on small heat shock proteins (sHSPs), a follow-up to successful workshops held in 2014, 2016 and 2018, took place as a virtual meeting on the 17-18 November 2022. The meeting was designed to provide an opportunity for those working on sHSPs to reconnect and discuss their latest work. The diversity of research in the sHSP field is reflected in the breadth of topics covered in the talks presented at this meeting.

Emotion-behaviour decoupling and experiential pleasure deficits predict negative symptoms and functional outcome in first-episode schizophrenia patients.

Background: Emotion-behaviour decoupling refers to the failure to translate emotion into motivated behaviour, and is a putative marker for schizophrenia. The heterogeneity of experiential pleasure and emotion expressivity deficits has been reported in schizophrenia patients. These three constructs are believed to contribute to negative symptoms, but very few studies have examined their predictive ability for clinical and functional outcome of schizophrenia.

Event-Based Clinical Finding Extraction from Radiology Reports with Pre-trained Language Model.

Radiology reports contain a diverse and rich set of clinical abnormalities documented by radiologists during their interpretation of the images. Comprehensive semantic representations of radiological findings would enable a wide range of secondary use applications to support diagnosis, triage, outcomes prediction, and clinical research. In this paper, we present a new corpus of radiology reports annotated with clinical findings.

Site-Selective Lysine Acetylation of Human Immunoglobulin G for Immunoliposomes and Bispecific Antibody Complexes.

Site-selective acetylation of a single lysine residue in a protein that reaches a lysine acetyltransferase's accuracy, precision, and reliability is challenging. Here, we report a peptide-guided, proximity-driven group transfer reaction that acetylates a single lysine residue, Lys 248, of the fragment crystallizable region (Fc region) in the heavy chain of the human Immunoglobulin G (IgG). An Fc-interacting peptide bound with the Fc domain and positioned a phenolic ester close to Lys 248, which induced a nucleophilic reaction and resulted in the transfer of an acetyl group to Lys 248.

The Important Role of Motivation and Pleasure Deficits on Social Functioning in Patients With Schizophrenia: A Network Analysis.

Negative symptoms, particularly the motivation and pleasure (MAP) deficits, are associated with impaired social functioning in patients with schizophrenia (SCZ). However, previous studies seldom examined the role of the MAP on social functioning while accounting for the complex interplay between other psychopathology. This network analysis study examined the network structure and interrelationship between negative symptoms (at the "symptom-dimension" and "symptom-item" levels), other psychopathology and social functioning in a sample of 269 patients with SCZ.

Automatic Assignment of Radiology Examination Protocols Using Pre-trained Language Models with Knowledge Distillation.

Selecting radiology examination protocol is a repetitive, and time-consuming process. In this paper, we present a deep learning approach to automatically assign protocols to computed tomography examinations, by pre-training a domain-specific BERT model (BERT). To handle the high data imbalance across exam protocols, we used a knowledge distillation approach that up-sampled the minority classes through data augmentation.

Prospective Memory Influences Social Functioning in People With First-Episode Schizophrenia: A Network Analysis and Longitudinal Study.

Prospective memory (PM) impairment is associated with impaired social functioning, but evidence is limited to chronic schizophrenia samples and cross-sectional design. The aim of this study was to utilize network analysis to address the complex interplay between PM, psychopathology, and functional outcome. This longitudinal study recruited 119 people with first-episode schizophrenia and followed up with them for 2 to 6 years.

A distinct giant coat protein complex II vesicle population in Arabidopsis thaliana.

Plants live as sessile organisms with large-scale gene duplication events and subsequent paralogue divergence during evolution. Notably, plant paralogues are expressed tissue-specifically and fine-tuned by phytohormones during various developmental processes. The coat protein complex II (COPII) is a highly conserved vesiculation machinery mediating protein transport from the endoplasmic reticulum to the Golgi apparatus in eukaryotes.

Non-coplanar VMAT plans for postoperative primary brain tumour to reduce dose to hippocampus, temporal lobe and cochlea: a planning study.

Objectives: This study aimed to compare radiotherapy plan quality of coplanar volumetric modulated arc therapy (CO-VMAT) and non-coplanar VMAT (NC-VMAT) for post-operative primary brain tumour.

Methods: A total of 16 patients who were treated for primary brain tumours were retrospectively selected for this study. For each patient, identical CT sets with structures were used for both CO-VMAT and NC-VMAT planning.

Derivation of a Ni bioaccessibility value for screening-level risk assessment of Ni substances in ingested materials including soils.

The objective of the present study was to derive a Ni bioaccessibility value for screening-level risk assessment of Ni substances in ingested materials including soils where multiple Ni substances are expected but not definitively identified. Broad ranges of Ni mass loading and dissolution time of a simple gastric assay were applied to pure Ni substances (removing the confounding factors of soil constituents on dissolution), thus broadening the applicability of the conclusions. The data were also used to support current knowledge of 'read across' for Ni substances.

Gastric bioaccessibility is a conservative measure of nickel bioavailability after oral exposure: Evidence from Ni-contaminated soil, pure Ni substances and Ni alloys.

Oral bioaccessibility (BAc) is a surrogate for the bioavailability (BAv) of a broad range of substances, reflecting the value that the approach offers for assessing oral exposure and risk. BAc is generally considered to have been validated as a proxy for oral BAv for the important soil contaminants Pb, Cd, and As. Here, using literature data for Ni BAc and BAv, we confirmed that Ni BAc (gastric only, with HCl mimicking stomach conditions) is a conservative measure of BAv for the oral exposure pathway.

Extraction and Analysis of Clinically Important Follow-up Recommendations in a Large Radiology Dataset.

Communication of follow-up recommendations when abnormalities are identified on imaging studies is prone to error. In this paper, we present a natural language processing approach based on deep learning to automatically identify clinically important recommendations in radiology reports. Our approach first identifies the recommendation sentences and then extracts reason, test, and time frame of the identified recommendations.

Structural Biology and Electron Microscopy of the Autophagy Molecular Machinery.

Autophagy is a highly regulated bulk degradation process that plays a key role in the maintenance of cellular homeostasis. During autophagy, a double membrane-bound compartment termed the autophagosome is formed through de novo nucleation and assembly of membrane sources to engulf unwanted cytoplasmic components and targets them to the lysosome or vacuole for degradation. Central to this process are the autophagy-related (ATG) proteins, which play a critical role in plant fitness, immunity, and environmental stress response.

Subnanometer resolution cryo-EM structure of ATG9.

Macroautophagy/autophagy is an essential process for the maintenance of cellular homeostasis by recycling macromolecules under normal and stress conditions. ATG9 (autophagy related 9) is the only integral membrane protein in the autophagy core machinery and has a central role in mediating autophagosome formation. In cells, ATG9 exists on mobile vesicles that traffic to the growing phagophore, providing an essential membrane source for the formation of autophagosomes.

Morphological Diversity, Protein Adsorption, and Cellular Uptake of Polydopamine-Coated Gold Nanoparticles.

Polydopamine (PDA)-coated nanoparticles are adhesive bionanomaterials widely utilized in intracellular applications, yet how their adhesiveness affects their colloidal stability and their interactions with serum proteins and mammalian cells remain unclear. In this work, we systematically investigate the combined effects of dopamine (DA) concentration and polymerization time (both reaction parameters spanning 2 orders of magnitude) on the morphological diversity of PDA-coated nanoparticles by coating PDA onto gold nanoparticle cores. Independent of the DA concentration, Au@PDA NPs remain largely aggregated upon several hours of limited polymerization; interestingly, extended polymerization for 2 days or longer yield randomly aggregated NPs, nearly monodisperse NPs, or worm-like NP chains in the ascending order of DA concentration.

Isolation of the Plant Exocyst Complex.

The exocyst, conserved from yeast to plants to mammals, is a hetero-octameric complex that mediates tethering of secretory vesicles to designated sites on the plasma membrane during polarized exocytosis. Because structural studies of the intact exocyst complex have been greatly limited by the low yields of purified proteins, many aspects of the exocyst functions remain poorly understood. Here, we present the protocols for the isolation and purification of the recombinant and the native plant exocyst complex.

Validation of site-specific soil Ni toxicity thresholds with independent ecotoxicity and biogeochemistry data for elevated soil Ni.

The Existing Substances Regulation Risk Assessments by the European Union (EU RA) generated new toxicity data for soil organisms exposed to Ni added to sixteen field-collected soils with low background concentration of metals and varying physico-chemical soil characteristics. Using only effective cation exchange capacity (eCEC) as a bioavailability correction, chronic toxicity of Ni in soils with a wide range of characteristics could be predicted within a factor of two. The objective of the present study was to determine whether this was also the case for three independent data sets of Ni toxicity thresholds.

Managed Care Peer-Led Teaching: An Innovative Learning Approach Outside the College of Pharmacy Core Curriculum.

Background: Managed care pharmacy is a growing field, but there are still limited educational opportunities available in pharmacy school core curricula. Students often seek self-directed learning opportunities to further explore the field.

Objectives: To (a) evaluate practicality and effectiveness of a student-designed managed care pharmacy elective and (b) determine emerging best practices for design and sustainability of peer-led, self-directed courses.

Structure of the human dimeric ATM kinase.

DNA-double strand breaks activate the serine/threonine protein kinase ataxia-telangiectasia mutated (ATM) to initiate DNA damage signal transduction. This activation process involves autophosphorylation and dissociation of inert ATM dimers into monomers that are catalytically active. Using single-particle electron microscopy (EM), we determined the structure of dimeric ATM in its resting state.

Chaperonin TRiC/CCT Modulates the Folding and Activity of Leukemogenic Fusion Oncoprotein AML1-ETO.

AML1-ETO is the most common fusion oncoprotein causing acute myeloid leukemia (AML), a disease with a 5-year survival rate of only 24%. AML1-ETO functions as a rogue transcription factor, altering the expression of genes critical for myeloid cell development and differentiation. Currently, there are no specific therapies for AML1-ETO-positive AML.

Molecular architecture of the Ub-PCNA/Pol η complex bound to DNA.

Translesion synthesis (TLS) is the mechanism by which DNA polymerases replicate through unrepaired DNA lesions. TLS is activated by monoubiquitination of the homotrimeric proliferating cell nuclear antigen (PCNA) at lysine-164, followed by the switch from replicative to specialized polymerases at DNA damage sites. Pol η belongs to the Y-Family of specialized polymerases that can efficiently bypass UV-induced lesions.

Modulation of STAT3 folding and function by TRiC/CCT chaperonin.

Signal transducer and activator of transcription 3 (Stat3) transduces signals of many peptide hormones from the cell surface to the nucleus and functions as an oncoprotein in many types of cancers, yet little is known about how it achieves its native folded state within the cell. Here we show that Stat3 is a novel substrate of the ring-shaped hetero-oligomeric eukaryotic chaperonin, TRiC/CCT, which contributes to its biosynthesis and activity in vitro and in vivo. TRiC binding to Stat3 was mediated, at least in part, by TRiC subunit CCT3.