Browse Articles

Molecular mechanisms of CBASS phospholipase effector CapV mediated membrane disruption

Identification of a free-N-glycan with difucosylated type-1 lactosamine in cancerous tissue and its validation for cancer diagnosis by urinary testing

Real world outcomes of faricimab in treatment resistant neovascular age-related macular degeneration among Asian patients

Development of an adeno-associated virus vector for gene replacement therapy of NF1-related tumors

Abstract Neurofibromatosis type 1 (NF1) is a tumor predisposition syndrome caused by alterations in NF1 gene that lead to tumor growth throughout the nervous system, which can cause morbidity and mortality, and transform to malignancy. NF1 gene replacement therapy, though promising, is hindered by NF1 gene’s large size and delivery challenges. We introduced a membrane-targeted, truncated neurofibromin comprising the GAP-related domain (GRD) fused to the KRAS4B C-terminal domain, which effectively inhibits the RAS signaling pathway and restores Schwann cell differentiation in an NF1 iPSC-derived model. For systemic application, we engineered an adeno-associated virus (AAV) vector using in vivo capsid evolution through sequential DNA shuffling and peptide library screening in a NF1 xenograft mouse model. This tailored vector, AAV-NF, exhibits greatly reduced liver uptake, enhanced tumor targeting across various NF1-related MPNST, neurofibromas and glioma models, and therapeutic efficacy in xenografts of MPNST. This study not only advances a viable AAV vector for NF1 treatment but also outlines a replicable strategy for vector and payload development in other monogenic and tumor-associated disease manifestations.

A hybrid deep learning model with feature engineering technique to enhance teacher emotional support on students’ engagement for sustainable education

Partners in root nodule symbiosis respond uniquely to heavy metal stresses in a host genotype-dependent manner

Abstract The mutualistic symbiosis between legume roots and soil rhizobia culminates in the formation of root nodules, where nitrogen is fixed. Root nodule symbiosis is inhibited by heavy metal stress. In this study, we investigated the relative responses of the symbiotic partners to a non-essential heavy metal cadmium (Cd) and an essential heavy metal zinc (Zn) stress and identified patterns in gene expression. We performed dual transcriptomics in nodules, using the Medicago truncatula-Sinorhizobium meliloti symbiotic system. Phenotypes were measured in the wild-type Medicago truncatula and a mutant in an ABC transporter gene ( Mtabcg36 ), which showed compromised nodule formation in control conditions and further after heavy metal treatment. We observed that the rhizobia were particularly sensitive to Zn in mutant nodules. The greatest degree of differential gene expression in the host plant were observed under Cd and Zn treatments in wild-type nodules. Most Cd-regulated host genes were also differentially regulated by Zn, revealing little discernment between an essential and a non-essential ion under increased exposure. Furthermore, the host response to both the stresses affected auxin and iron homeostasis genes in a host genotype-dependent manner. Our results suggested impaired cadmium export from the mutant nodules. These results have potential implications in agricultural management systems and bioremediation strategies.

Thermodynamic dissipation constrains metabolic versatility of unicellular growth

Abstract Metabolic versatility enables unicellular organisms to grow in vastly different environments. Since growth occurs far from thermodynamic equilibrium, the second law of thermodynamics has long been believed to pose key constraints to life. Yet, such constraints remain largely unknown. Here, we integrate published data spanning decades of experiments on unicellular chemotrophic growth and compute the corresponding thermodynamic dissipation. Due to its span in chemical substrates and microbial species, this dataset samples the versatility of metabolism. We find two empirical thermodynamic rules: first, the amount of energy dissipation per unit of biomass grown is largely conserved across metabolic types and domains of life; second, aerobic respiration exhibits a trade-off between dissipation and growth, reflecting in its high thermodynamic efficiency. By relating these rules to the fundamental thermodynamic forces that drive and oppose growth, our results show that dissipation imposes tight constraints on metabolic versatility.

A time-fractional model of hydromagnetic slip flow of viscous fluid in rotational frame with heat and mass transfer

Spontaneous calcium transients in hair cell stereocilia

Abstract The hair bundle of auditory and vestibular hair cells converts mechanical stimuli into electrical signals through mechanoelectrical transduction (MET). The MET apparatus is built around a tip link that connects neighboring stereocilia that are aligned in the direction of mechanosensitivity of the hair bundle. Upon stimulation, the MET channel complex responds to changes in tip-link tension and allows a cation influx into the cell. Ca2+ influx in stereocilia has been used as a signature of MET activity. Using genetically encoded Ca2+ sensors (GCaMP3, GCaMP6s) and high-performance fluorescence confocal microscopy, we detect spontaneous Ca2+ transients in individual stereocilia in developing and fully formed hair bundles. We demonstrate that this activity is abolished by MET channel blockers and thus likely originates from putative MET channels. We observe Ca2+ transients in the stereocilia of mice in tissue explants as well as in vivo in zebrafish hair cells, indicating this activity is evolutionarily conserved. Within stereocilia, the origin of Ca2+ transients is not limited to the canonical MET site at the stereocilia tip but is also present along the stereocilia length. Remarkably, we also observe these Ca2+ transients in the microvilli-like structures on the hair cell surface in the early stages of bundle development, prior to the onset of MET. Ca2+ transients are also present in the tallest rows of stereocilia in auditory hair cells, structures not traditionally thought to contain MET channels. We hypothesize that this newly described activity may reflect stochastic and spontaneous MET channel opening. Localization of these transients to other regions of the stereocilia indicates the presence of a pool of channels or channel precursors. Our work provides insights into MET channel assembly, maturation, function, and turnover. .

Dynamic cell fate plasticity and tissue reintegration drive functional adult synovial joint regeneration after complete resection

SETD5 in glioma cells conferred TRAIL resistance induction

Prevalence of anti-thyroid peroxidase antibodies among women with polycystic ovary syndrome

Mechano-crosstalk between living and artificial cells

The effect of productive capacity changes, income, and clean energy on ecological sustainability in China by novel KRLS approach

Potassium nitrate (kno₃) seed priming enhances soybean seed performance

Regulation of lattice oxygen reactivity of ZrO2 to promote efficient chemical looping oxidative dehydrogenation of ethane

MultiNet-IDS: an ensemble of DRL and LSTM for improved intrusion detection in wireless sensor networks

A machine learning approach for non-invasive PCOS diagnosis from ultrasound and clinical features

A membrane Sabatier system for water recovery and rocket propellant production

The climate benefit of a greener blue hydrogen

Abstract Previous studies have demonstrated the potential benefit of a future hydrogen economy in terms of reducing CO2 emissions. The hydrogen leakage rate and the green hydrogen fraction in the mix were identified as key factors in maximising the climate benefit of this energy transition. This study highlights the importance of blue hydrogen production hypotheses for a climate-beneficial transition to a hydrogen economy. The benefits are substantial when blue hydrogen is produced properly using an efficient CO₂ sequestration hydrogen production plant and minimizing the rate of upstream CH₄ leakage. The rate of hydrogen leakage remains an important parameter to consider throughout the entire value chain. Based on various scenarios of the development of a 21st century hydrogen economy, we estimate significant CO₂ emission reductions of 266–418 GtCO₂eq (up to 395–675 GtCO2eq in the case of a “high hydrogen demand” scenario) between 2030 and 2100. This cumulative reduction in CO₂ emissions translates into a reduction in global warming of 0.12–0.19 °C (0.18–0.30 °C for a “high hydrogen demand”) by the end of the century.