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Epiregulon: Single-cell transcription factor activity inference to predict drug response and drivers of cell states
Mechanically reliable and electronically uniform monolayer MoS2 by passivation and defect healing
Peptide-based rigid nanorod-reinforced gelatin methacryloyl hydrogels for osteochondral regeneration and additive manufacturing
KNN-based frequency-adjustable ferroelectric heterojunction and biomedical applications
Abstract High-performance lead-free K0.5Na0.5NbO3 piezoelectric ceramics present a practical alternative to lead-containing counterparts by effectively reducing potential environmental hazards. This advancement is particularly relevant to the development of ferroelectric heterojunction devices for biomedical applications. Here, we design and fabricate a frequency-adjustable ferroelectric heterojunction based on the developed K0.5Na0.5NbO3 piezoelectric ceramics with a high piezoelectric coefficient (d 33 = 680 pC/N). By leveraging flexible encapsulation, the heterojunction achieves miniaturization (φ = 13.3 mm, h = 2.28 mm) and suitability for implantation. After penetrating the rat skull, the ultrasound generated by the heterojunction at a frequency of 3 MHz reaches a focal depth of about 7.9 mm, a focal width of approximately 480 μm at −6 dB, and millimeter-scale continuous focal tuning (1.5 mm) within a narrow frequency range (2.7–3.3 MHz). Additionally, the implanted heterojunction enables long-term and high-precision transcranial neuromodulation, and consequently yields therapeutic effects in a myocardial infarction animal model. Collectively, this study highlights a viable strategy for developing and applying lead-free ferroelectric heterojunctions, expanding their potential in brain modulation, and providing new insights into clinical treatments of myocardial infarction.
Sporadic ALS induced pluripotent stem cell derived neurons reveal hallmarks of TDP-43 loss of function
High performance data integration for large-scale analyses of incomplete Omic profiles using Batch-Effect Reduction Trees (BERT)
Abstract Data from high-throughput technologies assessing global patterns of biomolecules (omic data), is often afflicted with missing values and with measurement-specific biases (batch-effects), that hinder the quantitative comparison of independently acquired datasets. This work introduces batch-effect reduction trees (BERT), a high-performance method for data integration of incomplete omic profiles. We characterize BERT on large-scale data integration tasks with up to 5000 datasets from simulated and experimental data of different quantification techniques and omic types (proteomics, transcriptomics, metabolomics) as well as other datatypes e.g., clinical data, emphasizing the broad scope of the algorithm. Compared to the only available method for integration of incomplete omic data, HarmonizR, our method (1) retains up to five orders of magnitude more numeric values, (2) leverages multi-core and distributed-memory systems for up to 11 × runtime improvement (3) considers covariates and reference measurements to account for severely imbalanced or sparsely distributed conditions (up to 2 × improvement of average-silhouette-width).
Skeletal editing of 4-arylpyrimidines into diverse nitrogen heteroaromatics via four-atom synthons
Eliminating lead-exposure in nebulization therapy by lead-free piezoelectric
Global assessment of current extinction risks and future challenges for turtles and tortoises
12,13-diHOME protects against the age-related decline in cardiovascular function via attenuation of CaMKII
Whole-exome sequencing analysis identifies risk genes for schizophrenia
Abstract Rare coding variants across many genes contribute to schizophrenia liability, but they have only been implicated in 12 genes at exome-wide levels of significance. To increase power for gene discovery, we analyse exome-sequencing data for rare coding variants in a new sample of 4650 schizophrenia cases and 5719 controls, and combine these with published sequencing data for a total of 28,898 cases, 103,041 controls and 3444 proband-parent trios. We identify associations for STAG1 and ZNF136 at exome-wide significance, genes that were previously implicated in schizophrenia by the SCHEMA study at a false discovery rate of 5%. We also find associations at a false discovery rate of 5% for six genes that did not pass this statistical threshold in the SCHEMA study (SLC6A1, PCLO, ZMYND11, BSCL2, KLC1 and CGREF1). Among these genes, SLC6A1 and KLC1 are associated with damaging missense variants alone. STAG1, SLC6A1, ZMYND11 and CGREF1 are also enriched for rare coding variants in other developmental and psychiatric disorders. Moreover, STAG1 and KLC1 have fine-mapped common variant signals in schizophrenia. These findings provide insights into the neurobiology of schizophrenia, including further evidence suggesting an aetiological role for disrupted chromatin organisation.
B cell maturation antigen (BCMA) is dispensable for the survival of long-lived plasma cells
Abstract The survival of antibody-secreting plasma cells is essential for long-lasting humoral immunity. BCMA is proposed to promote APRIL-mediated survival signals. However, extensive shedding of murine BCMA raises doubts about its role as a signaling receptor. To unequivocally establish BCMA’s function in plasma cell survival, we generate two BCMA-deficient mouse lines and examine antigen-specific plasma cells post-immunization. Contrary to previous reports, both BCMA-deficient mouse lines have comparable numbers of antigen-specific long-lived plasma cells following both protein and mRNA immunizations. Transcriptome analysis reveals no reduction in survival signaling upon BCMA deletion. Interestingly, BCMA-deficient mice show increased total plasma cell numbers in the bone marrow and mesenteric lymph nodes after boost immunizations. These results indicate that BCMA has no intrinsic role in maintaining long-lived plasma cells. Instead, we propose that BCMA’s function is limited to acting as a soluble decoy receptor for APRIL, thereby fine-tuning the plasma cell population size by limiting survival factor availability. Our findings thus provide a strong argument against the APRIL-BCMA axis being a central mechanism for plasma cell longevity.