Recent Findings Research Articles

Unraveling the negative charge-to-spin conversion in the Heusler alloy Co2FeSi

Recent discoveries of Heusler alloy achieve a strong advantage of the chemically disordered sample in the charge-to-spin conversion and attracted interests for spintronics applications. Here, we observe the negative charge-to-spin conversion in single magnetic layer of Co2FeSi/MgO and prove generations of σy and σx by spin-torque ferromagnetic resonance (ST-FMR). We also report that the change in charge-to-spin conversion efficiency could be controlled by chemical disordering. Furthermore, the thickness dependents of Co2FeSi demonstrated bulk effect is responsible for the generation of spin current. This study contributes to understanding the mechanisms of spin current generation from magnetic full Heusler alloy and also paves the way for the applications of magnetic memory and nonvolatile spin logic technologies.

Exosomal delivery of miR-200b-3p suppresses the growth of hepatocellular carcinoma cells by targeting ERG- and VEGF-mediated angiogenesis

Hepatocellular carcinoma (HCC) remains a lethal malignancy with limited treatment options. Recent discoveries have highlighted the pivotal role of miRNAs in HCC progression. We previously reported that the expression of miR-200b-3p was decreased in HCC cells and exosomal miR‐200b‐3p from hepatocytes inhibited angiogenesis by suppressing the expression of the endothelial transcription factor ERG (erythroblast transformation‐specific (ETS)‐related gene), leading to the hypothesis that the delivery of this miRNA may inhibit angiogenesis and suppress HCC growth in vivo. Here, we tested this hypothesis by using human HCC inoculation models. First, we transfected the human HepG2 HCC cells and established a stable cell line that overexpressed a high level of miR-200b-3p. When miR-200b-3p-overexpressing cells were injected into severe combined immunedeficiency (SCID)-beige mice, tumor growth was significantly reduced compared to tumors of control cells, with a reduction in the expression of ERG and vascular endothelial growth factor (VEGF) and subsequent angiogenesis. Intra-tumoral injection of exosomes containing high levels of miR-200b-3p also reduced the growth of parental HepG2 tumors with reduced ERG and VEGF expression and angiogenesis. These results validate the inhibitory role of miR-200b-3p in tumor angiogenesis, thereby suppressing HCC tumor growth, and provide a novel insight into its potential therapeutic application.

Functional characterization of the SDR42E1 reveals its role in vitamin D biosynthesis

Vitamin D deficiency poses a widespread health challenge, shaped by environmental and genetic determinants. A recent discovery identified a genetic regulator, rs11542462, in the SDR42E1 gene, though its biological implications remain largely unexplored. Our bioinformatic assessments revealed pronounced SDR42E1 expression in skin keratinocytes and the analogous HaCaT human keratinocyte cell lines, prompting us to select the latter as an experimental model. Employing CRISPR/Cas9 gene-editing technology and multi-omics approach, we discovered that depleting SDR42E1 showed a 1.6-fold disruption in steroid biosynthesis pathway (P-value = 0.03), considerably affecting crucial vitamin D biosynthesis regulators. Notably, SERPINB2 (P-value = 2.17 × 10−103), EBP (P-value = 2.46 × 10−13), and DHCR7 (P-value = 8.03 × 10−09) elevated by ∼2–3 fold, while ALPP (P-value <2.2 × 10−308), SLC7A5 (P-value = 1.96 × 10−215), and CYP26A1 (P-value = 1.06 × 10−08) downregulated by ∼1.5–3 fold. These alterations resulted in accumulation of 7-dehydrocholesterol precursor and reduction of vitamin D3 production, as evidenced by the drug enrichment (P-value = 4.39 × 10−06) and total vitamin D quantification (R2 = 0.935, P-value = 0.0016) analyses. Our investigation unveils SDR42E1's significance in vitamin D homeostasis, emphasizing the potential of precision medicine in addressing vitamin D deficiency through understanding its genetic basis.

Microfluidic systems for modeling digestive cancer: a review of recent progress.

Purpose. This review aims to highlight current improvements in microfluidic devices designed for digestive cancer simulation. The review emphasizes the use of multicellular 3D tissue engineering models to understand the complicated biology of the tumor microenvironment (TME) and cancer progression. The purpose is to develop oncology research and improve digestive cancer patients' lives.Methods. This review analyzes recent research on microfluidic devices for mimicking digestive cancer. It uses tissue-engineered microfluidic devices, notably organs on a chip (OOC), to simulate human organ function in the lab. Cell cultivation on modern three-dimensional hydrogel platforms allows precise geometry, biological components, and physiological qualities. The review analyzes novel methodologies, key findings, and technical progress to explain this field's advances.Results. This study discusses current advances in microfluidic devices for mimicking digestive cancer. Micro physiological systems with multicellular 3D tissue engineering models are emphasized. These systems capture complex biochemical gradients, niche variables, and dynamic cell-cell interactions in the tumor microenvironment (TME). These models reveal stomach cancer biology and progression by duplicating the TME. Recent discoveries and technology advances have improved our understanding of gut cancer biology, as shown in the review.Conclusion. Microfluidic systems play a crucial role in modeling digestive cancer and furthering oncology research. These platforms could transform drug development and treatment by revealing the complex biology of the tumor microenvironment and cancer progression. The review provides a complete summary of recent advances and suggests future research for field professionals. The review's major goal is to further medical research and improve digestive cancer patients' lives.

Applying an ELSI lens to real-world data and novel genomic insights for personalized mental healthcare.

Improving the understanding of the complex relationship between genetic predispositions, environmental influences, and sociocultural factors in the development and progression of mental illness is crucial for optimizing treatment efficacy and addressing longstanding health disparities. This paper discusses the ethical, legal, and social implications (ELSI) of recent advancements in biomedical research, particularly in genome-wide association studies (GWAS), phenome-wide association studies (PheWAS), and genome-wide environment interaction studies (GWEIS). Despite recent scientific progresses, challenges such as inadequate study methodology (e.g., correlational studies) and lack of diversity within study samples persist. Recent discoveries of several genetic variants of diseases, could augment and improve, or even challenge, existing understanding of the onset and management of mental illness. Leveraging real-world data (RWD), including electronic health record data (EHRs) focused on social determinant of health alongside biobank data, offers further opportunities to enhance the understanding of gene-environment interactions and inform efforts for reducing disparities in mental healthcare. Increased knowledge can support timely, holistic, evidence-based, and personalized care. Addressing ELSI considerations and maximizing the use of RWD is essential for advancing ethical and inclusive psychiatric genetics research, ultimately improving patient outcomes and promoting equitable access to evidence-based treatments.

Rational Design and Synthesis of CO2 Reduction Reaction Catalysts of High Faradaic Efficiency Toward C2 + Chemical Conversions

Carbon dioxide emission from fossil fuel combustion poses a major threat to global environment and ecological systems.Carbon capture, sequestration and conversion technologies are widely pursued as possible solutions to mitigate negative impact by CO2. The electrochemical CO2 reduction reaction (CO2RR) to fuels and chemicals using renewable electricity offers attractive “carbon-neutral” and “carbon-negative” mitigation strategies. Various catalysts have been investigated as the electrocatalysts for CO2RR. Key challenges facing the current catalyst and electrolyzer designs include insufficient energy efficiency and low single product selectivity.CO2RR to C2+ chemicals represent a highly important area for CO2 reduction and utilization. For example, ethanol, ethylene, propanol, etc. are among the most produced chemicals by the industry and are widely used for various applications. Using CO2 as raw material for chemical production through electrocatalysis not only improves the carbon cycling, but also reduces the overall emissions from chemical production. While CO2RR via two proton-electron pairs (PEPs), such as the conversion of CO2 to CO or formate, have been proven high selective with fast kinetics, conversions to C2+ chemicals are significantly more difficult due to the rapid escalation of required PEPs to much higher numbers (for example, 12 for ethanol and 18 for propanol), in addition to C-C bond coupling. The increased PEPs substantially complicate the conversion by required multiple steps along the electrochemical coordinate, leading to a high probability of branching reactions and low single product Faradaic efficiency (FE).To address these challenges, the design criteria for CO2RR to C2+ chemicals should be based on high uniformity of active center for directing identical catalytic path and suppressing competing reactions, strong catalyst-reactant binding in capturing the transient species through multiple PEP transfers, and microenvironment with nanoconfinement for retaining reaction intermediates during extended catalytic processes.Recently, we developed a new amalgamated lithium metal (ALM) synthesis method of preparing highly selective and active CO2RR catalyst and achieved > 90% FE for conversion of CO2 to ethanol [1]. Our have since expanded the approach to other C2 + chemicals including acetate, acetone, glycerol, isopropanol, etc., all with FE at or higher than 80%. To better formulate our catalyst design strategy, we not only measured the CO2RR performance over a variety of electrocatalysts, but also investigated their activity-structure relationship through advanced material characterizations, combined with the first-principle computation. We found many interesting properties uniquely associated to CO2RR mechanism and kinetics, such as catalyst-size and electro-potential modulated single selectivity. In this presentation, we will share our recent discoveries and future perspective on the development of highly selective CO2RR catalysts for C2+ chemical conversions. Acknowledgement: This work is supported by U. S. Department of Energy, Office of Energy Efficiency and Renewable Energy - Industrial Efficiency & Decarbonization Office and by Office of Science, U.S. Department of Energy under Contract DE-AC02-06CH11357.[1] “Highly selective electrocatalytic CO2 reduction to ethanol by metallic clusters dynamically formed from atomically dispersed copper” Haiping Xu, Dominic Rebollar, Haiying He, Lina Chong, Yuzi Liu, Cong Liu, Cheng-Jun Sun, Tao Li, John V. Muntean, Randall E. Winans, Di-Jia Liu and Tao Xu, (2020) Nature Energy, 5, 623–632

Coexistence and Interplay of Two Ferroelectric Mechanisms in Zn1-xMgxO.

Ferroelectric materials promise exceptional attributes including low power dissipation, fast operational speeds, enhanced endurance, and superior retention to revolutionize information technology. However, the practical application of ferroelectric-semiconductor memory devices has been significantly challenged by the incompatibility of traditional perovskite oxide ferroelectrics with metal-oxide-semiconductor technology. Recent discoveries of ferroelectricity in binary oxides such as Zn1-xMgxO and Hf1-xZrxO have been a focal point of research in ferroelectric information technology. This work investigates the ferroelectric properties of Zn1-xMgxO utilizing automated band excitation piezoresponse force microscopy. This findings reveal the coexistence of two ferroelectric subsystems within Zn1-xMgxO. A "fringing-ridge mechanism" of polarization switching is proposed that is characterized by initial lateral expansion of nucleation without significant propagation in depth, contradicting the conventional domain growth process observed in ferroelectrics. This unique polarization dynamics in Zn1-xMgxO suggests a new understanding of ferroelectric behavior, contributing to both the fundamental science of ferroelectrics and their application in information technology.

Early evolution of small body size in Homo floresiensis

Recent discoveries of Homo floresiensis and H. luzonensis raise questions regarding how extreme body size reduction occurred in some extinct Homo species in insular environments. Previous investigations at Mata Menge, Flores Island, Indonesia, suggested that the early Middle Pleistocene ancestors of H. floresiensis had even smaller jaws and teeth. Here, we report additional hominin fossils from the same deposits at Mata Menge. An adult humerus is estimated to be 9 − 16% shorter and thinner than the type specimen of H. floresiensis dated to ~60,000 years ago, and is smaller than any other Plio-Pleistocene adult hominin humeri hitherto reported. The newly recovered teeth are both exceptionally small; one of them bears closer morphological similarities to early Javanese H. erectus. The H. floresiensis lineage most likely evolved from early Asian H. erectus and was a long-lasting lineage on Flores with markedly diminutive body size since at least ~700,000 years ago.

Biomarker Landscape in RASopathies.

RASopathies are a group of related genetic disorders caused by mutations in genes within the RAS/MAPK signaling pathway. This pathway is crucial for cell division, growth, and differentiation, and its disruption can lead to a variety of developmental and health issues. RASopathies present diverse clinical features and pose significant diagnostic and therapeutic challenges. Studying the landscape of biomarkers in RASopathies has the potential to improve both clinical practices and the understanding of these disorders. This review provides an overview of recent discoveries in RASopathy molecular profiling, which extend beyond traditional gene mutation analysis. mRNAs, non-coding RNAs, protein expression patterns, and post-translational modifications characteristic of RASopathy patients within pivotal signaling pathways such as the RAS/MAPK, PI3K/AKT/mTOR, and Rho/ROCK/LIMK2/cofilin pathways are summarized. Additionally, the field of metabolomics holds potential for uncovering metabolic signatures associated with specific RASopathies, which are crucial for developing precision medicine. Beyond molecular markers, we also examine the role of histological characteristics and non-invasive physiological assessments in identifying potential biomarkers, as they provide evidence of the disease's effects on various systems. Here, we synthesize key findings and illuminate promising avenues for future research in RASopathy biomarker discovery, underscoring rigorous validation and clinical translation.

Emerging Trends and Innovations in the Treatment and Diagnosis of Atherosclerosis and Cardiovascular Disease: A Comprehensive Review towards Healthier Aging.

Cardiovascular diseases (CVDs) are classed as diseases of aging, which are associated with an increased prevalence of atherosclerotic lesion formation caused by such diseases and is considered as one of the leading causes of death globally, representing a severe health crisis affecting the heart and blood vessels. Atherosclerosis is described as a chronic condition that can lead to myocardial infarction, ischemic cardiomyopathy, stroke, and peripheral arterial disease and to date, most pharmacological therapies mainly aim to control risk factors in patients with cardiovascular disease. Advances in transformative therapies and imaging diagnostics agents could shape the clinical applications of such approaches, including nanomedicine, biomaterials, immunotherapy, cell therapy, and gene therapy, which are emerging and likely to significantly impact CVD management in the coming decade. This review summarizes the current anti-atherosclerotic therapies' major milestones, strengths, and limitations. It provides an overview of the recent discoveries and emerging technologies in nanomedicine, cell therapy, and gene and immune therapeutics that can revolutionize CVD clinical practice by steering it toward precision medicine. CVD-related clinical trials and promising pre-clinical strategies that would significantly impact patients with CVD are discussed. Here, we review these recent advances, highlighting key clinical opportunities in the rapidly emerging field of CVD medicine.

Residual Sketch Learning for a Feature-Importance-Based and Linguistically Interpretable Ensemble Classifier.

Motivated by both the commonly used "from wholly coarse to locally fine" cognitive behavior and the recent finding that simple yet interpretable linear regression model should be a basic component of a classifier, a novel hybrid ensemble classifier called hybrid Takagi-Sugeno-Kang fuzzy classifier (H-TSK-FC) and its residual sketch learning (RSL) method are proposed. H-TSK-FC essentially shares the virtues of both deep and wide interpretable fuzzy classifiers and simultaneously has both feature-importance-based and linguistic-based interpretabilities. RSL method is featured as follows: 1) a global linear regression subclassifier on all original features of all training samples is generated quickly by the sparse representation-based linear regression subclassifier training procedure to identify/understand the importance of each feature and partition the output residuals of the incorrectly classified training samples into several residual sketches; 2) by using both the enhanced soft subspace clustering method (ESSC) for the linguistically interpretable antecedents of fuzzy rules and the least learning machine (LLM) for the consequents of fuzzy rules on residual sketches, several interpretable Takagi-Sugeno-Kang (TSK) fuzzy subclassifiers are stacked in parallel through residual sketches and accordingly generated to achieve local refinements; and 3) the final predictions are made to further enhance H-TSK-FC's generalization capability and decide which interpretable prediction route should be used by taking the minimal-distance-based priority for all the constructed subclassifiers. In contrast to existing deep or wide interpretable TSK fuzzy classifiers, benefiting from the use of feature-importance-based interpretability, H-TSK-FC has been experimentally witnessed to have faster running speed and better linguistic interpretability (i.e., fewer rules and/or TSK fuzzy subclassifiers and smaller model complexities) yet keep at least comparable generalization capability.

Rethinking students' psychological need states: The unique role of need unfulfilment to understanding ill-being in academic settings.

Prior research has shown that students face various stressors which can affect their psychological health. The present study examines the role of students' psychological need states in explaining their burnout and dropout intentions. More precisely, relying on recent findings from Self-Determination Theory research, we examined whether students' psychological need unfulfilment could contribute to explain their ill-being over and above need satisfaction and frustration. To this end, we also tested the validity of a tripartite instrument allowing to assess these need states in academic settings (Psychological Need States in Education-Scale [PNSE-S]). A study was conducted among two samples of high school (N=473; Sample 1) and college (N=1143; Sample 2) students. Results supported the construct validity of the 35-item PNSE-S in both samples by showing that students' relatedness, autonomy, and competence unfulfilment can be modelled as distinct need states alongside the frustration and satisfaction of those three needs. Moreover, these different need states displayed a well-differentiated pattern of associations with various facets of student burnout and with dropout intentions. Results also showed the critical role of psychological need unfulfilment in explaining students' ill-being.

Application of Quercetin and its Novel Formulations in the Treatment of Malignancies of Central Nervous System: An Updated Review of Current Evidence based on Molecular Mechanisms.

Quercetin, a naturally occurring polyphenolic compound found in abundance in vegetables and fruits, has emerged as a compelling subject of study in cancer treatment. This comprehensive review delves into the significance and originality of quercetin's multifaceted mechanisms of action, with a particular focus on its application in various brain tumors such as glioblastoma, glioma, neuroblastoma, astrocytoma, and medulloblastoma. This review scrutinizes the distinctive facets of quercetin's anti-cancer properties, highlighting its capacity to modulate intricate signaling pathways, trigger apoptosis, impede cell migration, and enhance radiosensitivity in brain tumor cells. Significantly, it synthesizes recent research findings, providing insights into potential structure-activity relationships that hold promise for developing novel quercetin derivatives with heightened effectiveness. By unraveling the unique attributes of quercetin's anti-brain tumor effects and exploring its untapped potential in combination therapies, this review contributes to a deeper comprehension of quercetin's role as a prospective candidate for advancing innovative treatments for brain cancer.

The Chemical Puzzle of Weak G-Band Stars: A Comprehensive Study of HD 54627, HD 105783, HD 198718, and HD 201557

Weak G-band stars (WGBs) are a unique class of objects characterized by weak CH molecular lines in the Fraunhofer G band, indicative of a deficiency in 12C. This peculiar spectral feature is often accompanied by significant enrichments in N and, occasionally, Li and Na abundances. Despite their rarity and recent discoveries of new WGB candidates, the underlying formation mechanism of these stars remains unknown. In this study, we present a comprehensive chemical analysis of four neglected WGBs: HD 54627, HD 105783, HD 198718, and HD 201557. These stars, though identified as WGBs, have been poorly studied to date. Our analysis utilizes high-resolution échelle spectra with a power resolution of R ≈ 48,000, complemented by photometric and astrometric data from the literature. Applying the local thermodynamic equilibrium (LTE) approximation we determine the chemical abundance and then we conduct posterior non-LTE (NLTE) corrections for specific chemical abundances, including Li, O, Na, and Mg. Additionally, we provide details on the projected rotational velocities ( vsini ) and conduct a thorough investigation of the kinematics and orbits of our sample, comparing them with other well-studied WGBs reported in the literature. Our findings indicate that these stars originate from the thin disk, as evidenced by the absence of alpha-element enrichment and kinematics. Notably, half of the WGBs in our sample exhibit Li-rich characteristics, and we identify no rapid rotators ( vsini> 8.0 km s−1) or infrared excess among our studied stars.

Psilocybin in pharmacotherapy of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic mental disease that affects approximately 2% of the population. Obsessions and compulsions are troublesome for patients and may disturb their everyday activities. The pathogenesis of this disease is still not fully elucidated, but dysfunctions of serotonin-, dopamine- and glutamate-mediated neurotransmission together with early maladaptive schemas seem of importance. Pharmacological treatment includes drugs affecting the serotoninergic, dopaminergic, and glutamatergic systems, such as selective serotonin reuptake inhibitors (SSRIs). Providing that up to 40% of patients with OCD are resistant to the currently available medications, there is a need for novel and effective therapies. Recent discoveries suggest that psilocybin, a non-physically addictive psychoactive substance, may ameliorate disease symptoms. When used in appropriate doses and under strict clinical control, psilocybin appears as a valuable treatment for OCD. This narrative article provides a thorough overview of OCD's etiology, current treatment options, and the emerging evidence supporting psilocybin's efficacy in managing OCD symptoms.

Superelastic electromechanical behaviors in ferroelectric PbTiO[formula omitted] ceramics under coupled mechanical-electric fields: Higher-order piezoelectric constitutive equations from first-principles

With the recent discovery of superelastic behaviors of ferroelectric (piezoelectric) ceramics, understanding their non-linear mechanical and electromechanical responses under high stress and electric field conditions is crucial for engineering and designing advanced piezoelectric devices, such as ultrasmall actuator systems. In this study, we carry out first-principles finite electric field calculations to clarify the mechanical and electromechanical properties under the electric field for typical ferroelectric ceramics of PbTiO3. Superelastic-like non-linear deformation behavior is enhanced or suppressed depending on the electric field direction, suggesting the possible design of superelasticity. We clarified that positive and negative electric fields to spontaneous polarization promote and inhibit deformation due to strain loading, thereby providing tunable superelasticity. We also investigate the mechanical loading and electric field dependence of the piezoelectric coefficient of PbTiO3. The tunable piezoelectric response can be provided with a coupling of mechanical loading and electric field. Finally, we present higher-order piezoelectric constitutive equations applicable for superelastic-like non-linear deformations under an electric field. The present results will open promising paradigms for functional piezoelectric devices, and the proposed piezoelectric constitutive equations broaden the design scope through finite element method analysis.

Selective and non-selective evolutionary signatures found in the simplest replicative biological entities.

Mitoviruses, which are considered evolutionary relics of extinct alpha-proteobacteria RNA phages, represent one of the simplest self-replicating biological systems. This study aims to quantitatively describe genomes and identify potential genomic signatures that support the protein phylogenetic-based classification criterion. Genomic variables, such as mononucleotide and dinucleotide composition, codon usage bias, and minimal free energy derived from optimized predicted RNA secondary structure, were analyzed. From the values obtained, the main evolutionary pressures were discussed, indicating that natural selection plays a significant role in shaping mitovirus genomes. However, neutral evolution also makes a significant contribution. This study reveals a significant discovery of structural divergence in Kvaramitovirus. The energy minimization approach employed to study 2D folding in this study reveals a distinct spatial organization of their genomes, providing evidence for the hypothesis of a single evolutionary event of circularization in the most recent common ancestor of the lineage. This hypothesis was discussed in light of recent discoveries by other researchers that partially support the existence of mitoviruses with circular genomes. Finally, this study represents a significant advancement in the understanding of mitoviruses, as it quantitatively describes the nucleotide sequence at the family and genus taxonomic levels. Additionally, we provide hypotheses that can be experimentally validated to inspire new research and address the gaps in knowledge of this fascinating, basally divergent RNA virus lineage.

Scheelite as a microtextural and geochemical tracer of multistage ore-forming processes in skarn mineralization: A case study from the giant Xintianling W deposit, South China

The Xintianling deposit is one of the largest skarn-type scheelite deposit in China. Recent discoveries of quartz vein-type scheelite mineralization within the deposit have raised questions about its origin and the evolution of ore-forming fluids, hindering a comprehensive understanding of the ore-forming process. We investigate the microtextures, trace elements, and oxygen isotope compositions of scheelite from different stages in both skarn-type and quartz vein-type W mineralizations. Combined with apatite geochemistry and U–Pb dating, we determine the timing of quartz vein-type mineralization and the evolution of hydrothermal system. Based on detailed petrological observation, three types (seven subtypes) of scheelite and two types of apatite are identified. The Mo contents and Eu/Eu* ratios of scheelite, along with the Ce/Ce* ratios of apatite indicate the oxygen fugacity of fluids during the skarn metallogenic episode is generally higher than that during the quartz-vein metallogenic episode. Furthermore, the Y/Ho ratios and REE patterns of scheelite indicate the presence of at least three significant episodes of fluid influx and fluid-rock interactions throughout entire ore-forming process. The O isotope compositions of Sch C in the quartz vein-type metallogenic episode reveal that the ore-forming fluids originated from a magmatic source, and meteoric water was mixed into the system, leading to the precipitation of Sch C4. The Ap I and Ap II closely coexists with scheelite, from quartz-vein metallogenic episode yield consistent U–Pb ages within error of 160.4 ± 2.4 Ma and 158.4 ± 1.3 Ma, respectively, indicating a close genetic link between quartz vein-type W mineralization and the fine-grained porphyritic biotite granite. Our study highlights the significance of pulsed fluid exsolution and the combined effects of multiple mechanisms, including fluid-rock interaction, fluid mixing, and changes in physicochemical conditions, in the formation of large W deposits.

α-Mannosylated HLA-II glycopeptide antigens dominate the immunopeptidome of immortalised cells and tumour tissues.

Immunopeptides are cell surface-located protein fragments that aid our immune system to recognise and respond to pathogenic insult and malignant transformation. In this two-part communication, we firstly summarise and reflect on our recent discovery documenting that MHC-II-bound immunopeptides from immortalised cell lines prevalently carry N-glycans that differ from the cellular glycoproteome (Goodson, Front Immunol, 2023), data discussed at the 2023 SfG Annual Meeting. These findings are important as immunopeptide glycosylation remains poorly understood in immunosurveillance. The study also opened up new technical and biological questions that we address in the second part of this communication. Our study highlighted that the performance of the search engines used to detect glycosylated immunopeptides from LC-MS/MS data remains untested and, importantly, that little biochemical in vivo evidence is available to document the nature of glycopeptide antigens in tumour tissues. To this end, we compared the N-glycosylated MHC-II-bound immunopeptides that were reported from tumour tissues of 14 meningioma patients in the MSFragger-HLA-Glyco database (Bedran, Nat Commun, 2023) to those we identified with the commercial Byonic software. Encouragingly, the search engines produced similar outputs supporting that N-glycosylated MHC-II-bound immunopeptides are prevalent in meningioma tumour tissues. Consistent also with in vitro findings, the tissue MHC-II-bound immunopeptides were found to predominantly carry hyper-processed (paucimannosidic- and chitobiose core-type) and hypo-processed (oligomannosidic-type) N-glycans that varied in prevalence and distribution between patients. Taken together, evidence is emerging suggesting that α-mannosidic glycoepitopes abundantly decorate MHC-II-bound immunopeptides in both immortalised cells and tumour tissues warranting further research into their functional roles in immunosurveillance.

Dead or Alive? How Bursty Star Formation and Patchy Dust Can Cause Temporary Quiescence in High-redshift Galaxies

The recent discovery of a galaxy at z = 7.3 with undetected optical emission lines and a blue UV-to-optical continuum ratio in JWST spectroscopy is surprising and needs to be explained physically. Here, we explore two possibilities that could cause such a seemingly quiescent ∼5 × 108 M ⊙ galaxy in the early Universe: (i) stochastic variations in the star formation history (SFH) and (ii) the effect of spatially varying dust attenuation on the measured line and continuum emission properties. Both scenarios can play out at the same time to amplify the effect. A stochastic star formation model (similar to realistic SFHs from hydrodynamical simulations of similar-mass galaxies) can create such observed properties if star formation is fast-varying with a correlation time of <150 Myr given a reasonable burst amplitude of ∼0.6 dex. The total time spent in this state is less than 20 Myr, and the likelihood of such a state to occur over 500 Myr at z = 7 is ∼50% (consistent with current observations). On the other hand, we show that a spectrum with blue UV continuum and lack of emission lines can be reproduced by a blue+red composite spectrum. The UV continuum is emitted from dust-free density-bounded H ii regions (blue component), while the red component is a dust-obscured starburst with weakened emission lines due to strong differential dust attenuation between stellar and nebular emission. Future resolving far-infrared observations with the Atacama Large Millimeter/submillimeter Array will shed light on the latter scenario.