Browse Articles

Predicting noncoding RNA and disease associations using multigraph contrastive learning

Fam102a translocates Runx2 and Rbpjl to facilitate Osterix expression and bone formation

AbstractBone remodeling maintains the robustness of the bone tissue by balancing bone resorption by osteoclasts and bone formation by osteoblasts. Although these cells together play a crucial role in bone remodeling, only a few reports are available on the common factors involved in the differentiation of the two types of cells. Here, we show family with sequence similarity 102 member A (Fam102a) as a bone-remodeling factor that positively regulates both osteoclast and osteoblast differentiation. Fam102a regulates osteoblast differentiation by controlling recombination signal binding protein for immunoglobulin κ J region-like (Rbpjl). The Fam102a-Rbpjl axis promotes the nuclear translocation of transcription factors and enhances the expression of Osterix, a transcription factor essential for osteoblast differentiation. The deletion of Fam102a or a functional mutation in Rbpjl leads to osteopenia accompanied by reduced osteoblastic bone formation. Thus, the Fam102a-Rbpjl axis plays an important role in osteoblasts and this finding provides insights into bone remodeling.

PathCrisp: an innovative molecular diagnostic tool for early detection of NDM-resistant infections

Assessment of soil classification based on cone penetration test data for Kaifeng area using optimized support vector machine

Enterocyte-like differentiation defines metabolic gene signatures of CMS3 colorectal cancers and provides therapeutic vulnerability

Scalable fabrication of an array-type fixed-target device for automated room temperature X-ray protein crystallography

Nicotinamide mononucleotide boosts the development of bovine oocyte by enhancing mitochondrial function and reducing chromosome lagging

Evidence for saddle point-driven charge density wave on the surface of heavily hole-doped iron arsenide superconductors

AbstractUnconventional superconductivity is known for its intertwining with other correlated states, making exploration of the intertwined orders important for understanding its pairing mechanism. In particular, spin and nematic orders are widely observed in iron-based superconductors; however, the presence of charge order is uncommon. Using scanning tunnelling microscopy, and through expanding the phase diagram of iron-arsenide superconductor Ba1−xKxFe2As2 to the hole-doping regime beyond KFe2As2 by surface doping, we demonstrate the formation of a charge density wave (CDW) on the arsenide surface of heavily hole-doped Ba1−xKxFe2As2. Its emergence suppresses superconductivity completely, indicating their direct competition. Notably, the CDW emerges when the saddle points approach the Fermi level, where its wavevector matches with those linking the saddle points, suggesting saddle-point nesting as its most probable formation mechanism. Our findings offer insights into superconductivity and intertwined orders, and a platform for studying them in iron-based superconductors close to the half-filled configuration.

Multienzyme cascade for synthesis of hydroxytyrosol via engineered Escherichia coli

Parametric optimization of flow in a solar chimney power plant under variable semi elliptical constraints

Nucleus-translocated GCLM promotes chemoresistance in colorectal cancer through a moonlighting function

AbstractMetabolic enzymes perform moonlighting functions during tumor progression, including the modulation of chemoresistance. However, the underlying mechanisms of these functions remain elusive. Here, utilizing a metabolic clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 knockout library screen, we observe that the loss of glutamate-cysteine ligase modifier subunit (GCLM), a rate-limiting enzyme in glutathione biosynthesis, noticeably increases the sensitivity of colorectal cancer (CRC) cells to platinum-based chemotherapy. Mechanistically, we unveil a noncanonical mechanism through which nuclear GCLM competitively interacts with NF-kappa-B (NF-κB)-repressing factor (NKRF), to promote NF-κB activity and facilitate chemoresistance. In response to platinum drug treatment, GCLM is phosphorylated by P38 MAPK at T17, resulting in its recognition by importin a5 and subsequent nuclear translocation. Furthermore, elevated expression of nuclear GCLM and phospho-GCLM correlate with an unfavorable prognosis and poor benefit from standard chemotherapy. Overall, our work highlights the essential nonmetabolic role and posttranslational regulatory mechanism of GCLM in enhancing NF-κB activity and subsequent chemoresistance.

Sex differences in aggression and its neural substrate in a cichlid fish

AbstractAggression is ubiquitous among social species and can function to maintain social dominance hierarchies. The African cichlid fish Astatotilapia burtoni is an ideal study species for studying aggression due to their dominance hierarchy and robust behavioral repertoire. To further understand the potential sex differences in aggression in this species, we characterized aggression in male and female A. burtoni in a mirror assay. We then quantified neural activation patterns in brain regions of the social behavior network (SBN) to investigate if differences in behavior are reflected in the brain with immunohistochemistry by detecting the phosphorylated ribosome marker phospho-S6 ribosomal protein (pS6), a marker for neural activation. We found that A. burtoni perform both identical and sex-specific aggressive behaviors in response to a mirror assay. Females had greater pS6 immunoreactivity than males in the Vv (ventral part of the ventral telencephalon), a homolog of the lateral septum in mammals. Males but not females had higher pS6 immunoreactivity in the ATn after the aggression assay. The ATn (anterior tuberal nucleus) is a homolog of the ventromedial hypothalamus in mammals, which is strongly implicated in the regulation of aggression in males. Several regions also have higher pS6 immunoreactivity in negative controls than fish exposed to a mirror, implicating a role for inhibitory neural processes in suppressing aggression until a relevant stimulus is present. Male and female A. burtoni display both similar and different behavioral patterns in aggression in response to a mirror assay. There are also sex differences in the corresponding neural activation patterns in the SBN. In mirror males but not females, the ATn clusters with the POA, revealing a functional connectivity of these regions that is triggered in an aggressive context in males. These findings suggest that distinct neural circuitry underlie aggressive behavior in male and female A. burtoni, serving as a foundation for future work investigating the molecular and neural underpinnings of sex differences in behavior in this species to reveal fundamental insights into understanding aggression.

Newton–Simpson-based predictor–corrector methods for milling chatter stability prediction

Characterization and structural analysis of a versatile aromatic prenyltransferase for imidazole-containing diketopiperazines

Drug discovery and mechanism prediction with explainable graph neural networks

Plasma concentration of MMP-17 is elevated in boys with cryptorchidism and correlates with HSP-70

Glia detect and transiently protect against dendrite substructure disruption in C. elegans

The analysis on forest farmers’ intention to participate in construction of the National Reserve Forest Project and its driving factors

Fault diagnosis of rotating parts integrating transfer learning and ConvNeXt model

Compound electron acceleration at planetary foreshocks

AbstractShock waves, the interface of supersonic and subsonic plasma flows, are the primary region for charged particle acceleration in multiple space plasma systems, including Earth’s bow shock, which is readily accessible for in-situ measurements. Spacecraft frequently observe relativistic electron populations within this region, characterized by energy levels surpassing those of solar wind electrons by a factor of 10,000 or more. However, mechanisms of such strong acceleration remain elusive. Here we use observations of electrons with energies up to 200 kiloelectron volts and a data-constrained model to reproduce the observed power-law electron spectrum and demonstrate that the acceleration by more than 4 orders of magnitude is a compound process including a complex, multi-step interaction between more commonly known mechanisms and resonant scattering by several distinct plasma wave modes. The proposed model of electron acceleration addresses a decades-long issue of the generation of energetic (and relativistic) electrons at planetary plasma shocks. This work may further guide numerical simulations of even more effective electron acceleration in astrophysical shocks.