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Revolutionizing Alzheimer’s disease detection with a cutting-edge CAPCBAM deep learning framework
An air target intention data extension and recognition model based on deep learning
Museomics of an extinct European flat oyster population
Abstract Understanding the factors that predispose species and populations to decline and extinction is a major challenge of biodiversity research. In the present study, we investigated the historical population genomics of an extinct population of the European oyster ( Ostrea edulis L.) from the Wadden Sea collected between 1868 and 1888, and compared it to French and English populations sampled at the same time. Our museomic results indicate that the now-extinct population was genetically isolated from the French and English populations and showed signs of local adaptation in the form of Fst outlier loci between the Wadden Sea and the other two populations. Thus the Wadden Sea oysters may have been predisposed for extinction because they were not naturally replenished from other populations. A comparison of population-wide genomic diversity may hint towards a sudden population contraction of the Wadden Sea population, possibly being the result of stronger - or earlier - population decline in this population than in the others. In summary, our historical population genomic exploration hints at some potential causes of population decline in flat oysters from the Wadden Sea, which might have led to their extinction.
Legume-based rotation enhance long-term soil carbon storage in eastern Oregon dryland wheat systems
An integrated mechanism of G <sub>q</sub> regulation of PLCβ enzymes
Phospholipase Cβ (PLCβ) enzymes are the principal effectors activated by G q heterotrimers. Both Gα q and Gβγ subunits can activate PLCβ, which requires precise positioning of PLCβ at the plasma membrane to relieve structural autoinhibition and give the active site access to the phosphatidylinositol 4,5-bisphosphate (PIP2) substrate. PLCβ enzymes possess a unique distal C-terminal domain (dCTD) that is critical for activation by Gα q , but the reason for this is unclear. It is also not known how G protein activation affects the subcellular localization of PLCβ enzymes, some of which are found primarily in the cytosol despite needing to act at the plasma membrane. Here, we use bioluminescence spectroscopy, imaging, and gene editing to study the membrane disposition of PLCβ enzymes in living cells and to define the functional roles of the dCTD. We find that PLCβ translocates to the plasma membrane upon G q activation, primarily by binding to Gα q subunits. This is rapidly counteracted by PIP2 hydrolysis, which promotes PLCβ translocation back into the cytosol. PLCβ translocation and activation require binding of Gα q to the catalytic domain and the dCTD at two distinct interfaces. Gα q binding to the dCTD is required for activation even when PLCβ is artificially tethered to the plasma membrane, suggesting that this domain has functions beyond simply recruiting the enzyme to the PIP2 substrate. We propose that in addition to associating PLCβ with the plasma membrane, the dCTD reorders the αN helix of active Gα q and thus participates directly in the precise positioning of the catalytic domain.
Electrolyte disorders in the critically ill: a retrospective analysis
Abstract Several electrolyte disorders have been associated with adverse outcomes, but data on the coincidence of multiple disorders, interactions between different electrolytes and the impact of substitution on electrolyte levels are scarce. This study aimed to describe electrolyte disorders’ prevalence, incidence, and interaction in a consecutive cohort of ICU patients. Single-center retrospective study, including 2,056 consecutive adult ICU patients. Patients without laboratory data, those declining participation, and those receiving renal replacement therapy were excluded. Electrolyte levels and intravenous electrolyte administration were analyzed during the first 96 h after ICU admission using descriptive statistics, regression models and AUC-ROC analysis. Of 2392 admitted patients, 2056 were included. On admission, 312 patients (15.2%) had no electrolytes measured, 316 (15.4%) did not have any electrolyte disorder, 643 (31.3%) had one disorder, and 785 (38.2%) had multiple disorders. The most common electrolyte disorders on admission were hyperchloremia (56.0%, 977/1,744), hyperkalemia (18.7%, 326/1,744), hypophosphatemia (16.8%, 293/1,744), and hyperphosphatemia (16.4%, 286/1,744). Most patients (77.4%, 1,592/2,056) developed at least one new disorder during their ICU stay. A considerable number of patients (19.7%, 344/1,744) experienced electrolyte disorders in both directions (‘hypo’ and ‘hyper’) during their ICU stay. Linear regression models revealed that changes in one electrolyte level are often associated with alterations in other electrolyte levels. Most patients (99.2% 2,039/2,056) received intravenous electrolytes. Electrolyte overcorrection occurred in 89/365 patients (24.4%) for hypokalemia and 50/575 patients (8.7%) for hypophosphatemia. AUC-ROC analysis revealed cut-off points with the highest sensitivity and specificity at 30 mmol of potassium within 6 h and 45 mmol of phosphate within 15 h. Electrolyte disorders are highly prevalent in ICU patients, with significant co-incidence and interplay between these disorders. Knowledge regarding overcorrection risks may inform safe electrolyte administration protocols.
<i>miR-155</i> impairs ICOSL and MHC-I expression in DLBCL lymphomas
Elevated miR-155 levels in B cell malignancies, such as CLL and DLBCL, correlate with increased aggressiveness of the disease. We recently reported that, in two different mouse models of miR-155 -driven B cell malignancy, miR-155 targets and down-regulates transcripts encoding ICOSL, the ligand for the Inducible T cell costimulator (ICOS), thereby impairing the capacity of T lymphocytes to recognize and eliminate malignant cells. In this report, we extend our previous findings to Human by showing that miR-155 levels negatively correlate with those of both ICOSL and MHC-I in samples from DLBCL patients. We present evidence of miR-155 reducing the levels of ICOSL transcripts in ABC, but not in GCB primary tumors (PTs) and cell lines (CLs). In contrast, there was no evidence of miR-155 targeting MHC-I transcript levels in both types of DLBCLs. Nevertheless, miR-155 and MHC-I levels inversely correlated in DLBCLs samples, suggesting the existence of indirect regulatory effects of miR-155 . There was also evidence of dose-dependent effects at low miR-155 levels. Altogether, our findings indicate that the deficiency of both ICOSL and MHC-I activity, driven by high levels of miR-155 , may be causative in the failure of the host immune system to recognize and eliminate malignant B cells.
Infrared thermography-based radiomics for early detection of metabolic syndrome
Abstract Radiomics is increasingly utilized in medical image analysis. This study evaluates the use of infrared thermography, a technique well-suited for radiomic analysis, in diagnosing metabolic syndrome (MS). Facial and palmar thermographs from 200 males (100 healthy controls and 100 MS patients) were analyzed. The dataset was split into a training cohort (n = 140) and a validation cohort (n = 60). All participants underwent laboratory testing on the same day as infrared thermography imaging. A total of 1656 radiomic features were extracted from each participant’s thermographs and refined using Pearson correlation coefficients, two-sample t-tests, and LASSO regression. A binary random forest (RF) classification model was then constructed and evaluated based on its calibration, discrimination, and clinical utility. The RF model demonstrated strong diagnostic performance, achieving an AUC of 0.91 in the validation cohort. Calibration and decision curve analyses confirmed the model’s clinical applicability. Infrared thermography-based radiomics offers a promising, non-invasive method for early screening of MS, highlighting its potential clinical utility.
Thermotropic reentrant isotropic symmetry and induced smectic antiferroelectricity in the ferroelectric nematic material RM734
We report a transition from the ferroelectric nematic liquid crystal (N F ) phase to a lower-temperature, apolar fluid phase having reentrant isotropic symmetry (I R ), in the liquid crystal compound RM734 doped with small concentrations of the ionic liquids 1-Butyl-3-methylimidazolium hexafluorophosphate (BMIM-PF 6 ) or 1-Ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EMIM-TFSI). Even a trace amount of ionic liquid dopant facilitates the kinetic pathway for the transition from the N F to the I R , enabling simple cooling to produce this isotropic fluid phase rather than resulting in immediate crystallization. The I R was also obtained in the absence of specific ionic liquid doping by appropriate temperature cycling in three distinct, as-synthesized-and-purified batches of RM734, two commercial and one from our laboratory. Ionic liquid doping also stabilizes the smectic Z A , an additional birefringent antiferroelectric phase having the director parallel to fluid smectic layers, significantly increasing its temperature range between the paraelectric and ferroelectric nematic phases with increasing BMIM concentration.
Carbon dioxide solubility in polyethylene glycol polymer: an accurate intelligent estimation framework
Force spectroscopy reveals membrane fluctuations and surface adhesion of extracellular nanovesicles impact their elastic behavior
The elastic properties of nanoscale extracellular vesicles (EVs) are believed to influence their cellular interactions, thus having a profound implication in intercellular communication. However, accurate quantification of their elastic modulus is challenging due to their nanoscale dimensions and their fluid-like lipid bilayer. We show that the previous attempts to develop atomic force microscopy-based protocol are flawed as they lack theoretical underpinning as well as ignore important contributions arising from the surface adhesion forces and membrane fluctuations. We develop a protocol comprising a theoretical framework, experimental technique, and statistical approach to accurately quantify the bending and elastic modulus of EVs. The method reveals that membrane fluctuations play a dominant role even for a single EV. The method is then applied to EVs derived from human embryonic kidney cells and their genetically engineered classes altering the tetraspanin expression. The data show a large spread; the area modulus is in the range of 4 to 19 mN/m and the bending modulus is in the range of 15 to 33 k B T , respectively. Surprisingly, data for a single EV, revealed by repeated measurements, also show a spread that is attributed to their compositionally heterogeneous fluid membrane and thermal effects. Our protocol uncovers the influence of membrane protein alterations on the elastic modulus of EVs.
In-depth analysis of magnetic flux concentration indicator in novel curved slots of multi-tooth dual-PM doubly salient machine
Abstract Multi-tooth structure in dual-PM doubly salient machine (MT-DDSPM) has discovered large flux leakage with a non-concentrated magnetic flux due to many square teeth and many edges at teeth and poles. To overcome these shortcomings, this paper proposed a novel design of the curved slots applied in the MT-DDSPM. In addition, the magnetic flux concentration indicator (MFCI) was originally formulated to measure the magnetic flux concentration at the stator teeth, focused mainly on the edge and slots. These aimed to optimize the design of curved slots applied in the 12/3/35-pole MT-DDSPM for superior torque production. The electromagnetic performance of the designed MT-DDSPM was deeply investigated using the finite element method in comparison to traditional square-slot design. The invented MT-DDSPM with curved slots revealed the highest MFCI of 25.47 compared to 19.16 obtained with the square slots. The results indicated an enhanced magnetic flux concentration of MT-DDSPM, leading to higher flux linkage and other electromagnetic performances. Especially, the rated torque obtained from the curved-slot design was 66.01% higher than the square one at the same rated current, providing a better profile even at overload current. The minimum ripple torque of 1.35% was found with the curved-slot MT-DDSPM. In conclusion, this work highlighted the superior performance of a novel curved-slot MT-DDSPM and provided a reliable alternative to evaluate the quality of magnetic flux concentration in terms of MFCI, which can be essential for the in-depth analysis of the multi-tooth family of electrical machines and relevant applications.
Unified molecular approach for spatial epigenome, transcriptome, and cell lineages
Spatial epigenomics and multiomics can provide fine-grained insights into cellular states but their widespread adoption is limited by the requirement for bespoke slides and capture chemistries for each data modality. Here, we present SPatial assay for Accessible chromatin, Cell lineages, and gene Expression with sequencing (SPACE-seq), a method that utilizes polyadenine-tailed epigenomic libraries to enable facile spatial multiomics using standard whole transcriptome reagents. Applying SPACE-seq to a human glioblastoma specimen, we reveal the state of the tumor microenvironment, extrachromosomal DNA copy numbers, and identify putative mitochondrial DNA variants.
Significance of miR-1290 in glioblastoma patients with epilepsy
Correction to Supporting Information for Li et al., Primed 3D injectable microniches enabling low-dosage cell therapy for critical limb ischemia
Molecular characterization and virulence of fungal pathogens associated with mass mortalities in hilsa Shad (Tenualosa ilisha)
MFRP is a molecular hub that organizes the apical membrane of RPE cells by engaging in interactions with specific proteins and lipids
Membrane frizzled-related protein (MFRP), present in the retinal pigment epithelium (RPE), is an integral membrane protein essential for ocular development and the normal physiology of the retina. Mutations in MFRP are associated with autosomal recessive nonsyndromic nanophthalmos, leading to severe hyperopia and early-onset retinitis pigmentosa. While several preclinical gene-augmentation and gene-editing trials hold promise for future therapies aimed at stopping degeneration and restoring retinal function, the molecular mechanisms involved in MFRP biology are still not well understood. Here, we studied the biochemical properties of MFRP and the molecular consequences of its loss of function in the retinal degeneration 6 (rd6) mouse model. Using transcriptomic and lipidomic approaches, we observed that accumulation of docosahexaenoic acid (DHA) constitutes a primary defect in the MFRP-deficient RPE. In biochemical assays, we showed that MFRP undergoes extensive glycosylation, and it preferentially binds lipids of several classes, including phosphatidylserine and phosphatidylinositol-4-phosphate; as well as binding to several transmembrane proteins, notably adiponectin receptor 1 (ADIPOR1) and inward rectifier potassium channel 13 (KCNJ13). Moreover, MFRP determines the subcellular localization of ADIPOR1 and KCNJ13 in the RPE in vivo. This feature is altered by MFRP deficiency and can be restored by gene-therapy approaches. Overall, our observations suggest that MFRP constitutes an important interaction hub within the apical membrane of RPE cells, coordinating protein trafficking and subcellular localization within the RPE, and lipid homeostasis within the entire retina.
A novel approach in using insect-based spinach-food waste for gene targeting to cancer tissues
Bidirectional disruption of <i>GNAS</i> transcripts causes broad methylation defects in pseudohypoparathyroidism type 1B
Pseudohypoparathyroidism type 1B (PHP1B) is a multihormone resistance disorder caused by aberrant GNAS methylation. Characteristic epigenetic changes at GNAS differentially methylated regions (DMRs), i.e., NESP, AS1, AS2, XL, and A/B, are associated with specific structural defects in different autosomal dominant PHP1B (AD-PHP1B) subtypes. However, mechanisms underlying abnormal GNAS methylation remain incompletely defined, largely because viable PHP1B mouse models are lacking. Using lymphoblastoid cells and induced pluripotent stem cells, we show that various GNAS methylation patterns in PHP1B reflect differential disruption of sense and antisense GNAS transcripts. In cases with broad GNAS methylation changes, loss of the maternal, sense-transcribed exon H/AS region impairs methylation of the AS1 DMR, which results in biallelic expression of an antisense transcript, GNAS-AS1 , and NESP hypermethylation. In contrast, cases with normal AS1 methylation, including STX16 deletions, show monoallelic GNAS-AS1 expression and normal NESP methylation. The roles of these GNAS transcripts were confirmed by a retrotransposon in GNAS-AS1 intron 1, identified in an AD-PHP1B family. This insertion impaired exon H/AS transcription when located on the maternal allele, thus preventing the complete establishment of methylation at all maternal GNAS DMRs, leading to biallelic GNAS-AS1 transcription. However, maternal GNAS-AS1 transcription was profoundly attenuated, thus allowing only a small gain-of-methylation at NESP. Likewise, on the paternal allele, the retrotransposon attenuated GNAS-AS1 transcription, thus preventing complete NESP methylation. Our findings support a model of bidirectional transcription-mediated regulation of methylation at GNAS DMRs and will help to refine systematic approaches for establishing molecular defects underlying different PHP1B subtypes.