New understandings of the genetic regulatory relationship between non-coding RNAs and m6A modification

One of the most frequent epigenetic modifications of RNA in eukaryotes is N6 methyladenosine (m6A), which is mostly present in messenger RNAs. Through the influence of several RNA processing stages, m6A modification is a crucial approach for controlling gene expression, especially in cancer progression. It is universally acknowledged that numerous non-coding RNAs (ncRNAs), such as microRNAs, circular RNAs, long non-coding RNAs, and piRNAs, are also significantly affected by m6A modification, and the complex genetic regulatory relationship between m6A and ncRNAs plays a pivotal role in the development of cancer. The connection between m6A modifications and ncRNAs offers an opportunity to explore the oncogene potential regulatory mechanisms and suggests that m6A modifications and ncRNAs could be vital biomarkers for multiple cancers. In this review, we discuss the mechanisms of interaction between m6A methylation and ncRNAs in cancer, and we also summarize diagnostic and prognostic biomarkers for clinical cancer detection. Furthermore, our article includes some methodologies for identifying m6A sites when assessing biomarker potential

Palmitoylation Regulates Intracellular Trafficking of β\u3csub\u3e2\u3c/sub\u3e Adrenergic Receptor/Arrestin/Phosphodiesterase 4D Complexes in Cardiomyocytes

β2 adrenergic receptor (β2AR) is a prototypical G-protein coupled receptor that stimulates the classic cAMP-protein kinase A (PKA) signaling pathway. Recent studies indicate that the cAMP-PKA activities are spatiotemporally regulated in part due to dynamic association of β2AR with phosphodiesterase 4D (PDE4D), a group of cAMP degradation enzymes. Here, we demonstrate that in cardiomyocytes, palmitoylation of β2AR, the covalent acylation of cysteine residue 341, plays a critical role in shaping subcellular cAMP-PKA activities in cardiomyocytes via regulating β2AR association with arrestin/PDE4D. Replacing cysteine 341 on β2AR with alanine (C341A) leads to an impaired binding to β arrestin 2. Surprisingly, the C341A mutant is able to internalize via an arrestin-independent pathway at saturated concentration of agonist stimulation; the internalization becomes caveolae-dependent and requires dynamin GTPase. However, the impaired binding to β arrestin 2 also leads to an impaired recruitment of PDE4D to the C341A mutant. Thus, the mutant C341A β2AR is transported alone from the plasma membrane to the endosome without recruiting PDE4D. This alteration leads to an enhanced cytoplasmic cAMP signal for PKA activation under β2AR stimulation. Functionally, Mutation of the C341 residue or inhibition of palmitoylation modification of β2AR enhances the receptor-induced PKA activities in the cytoplasm and increases in myocyte contraction rate. Our data reveal a novel function of palmitoylation in shaping subcellular cAMP-PKA signaling in cardiomyocytes via modulating the recruitment of β arrestin 2-PDE4D complexes to the agonist-stimulated β2AR

Contrast-enhanced fluorescence microscope by LED integrated excitation cubes

Fluorescence microscopy is a powerful tool for scientists to observe the microscopic world, and the fluorescence excitation light source is one of the most critical components. To compensate for the short operation lifetime, integrated light sources, and low excitation efficiency of conventional light sources such as mercury, halogen, and xenon lamps, we designed an LED-integrated excitation cube (LEC) with a decentralized structure and high optical power density. Using a Fresnel lens, the light from the light-emitting diode (LED) was effectively focused within a 15 mm mounting distance to achieve high-efficiency illumination. LEC can be easily designed in the shape of fluorescence filter cubes for installation in commercial fluorescence microscopes. LECs’ optical efficiency is 1–2 orders of magnitude higher than that of mercury lamps; therefore, high-quality fluorescence imaging with spectral coverage from UV to red can be achieved. By replacing conventional fluorescence filter cubes, LEC can be easily installed on any commercial fluorescence microscope. A built-in LEC driver can identify the types of LEDs in different spectral bands to adopt the optimal operating current and frequency of pulses. Moreover, high-contrast images can be achieved in pulse mode by time-gated imaging of long-lifetime luminescence

HelixFold-Single: MSA-free Protein Structure Prediction by Using Protein Language Model as an Alternative

AI-based protein structure prediction pipelines, such as AlphaFold2, have achieved near-experimental accuracy. These advanced pipelines mainly rely on Multiple Sequence Alignments (MSAs) as inputs to learn the co-evolution information from the homologous sequences. Nonetheless, searching MSAs from protein databases is time-consuming, usually taking dozens of minutes. Consequently, we attempt to explore the limits of fast protein structure prediction by using only primary sequences of proteins. HelixFold-Single is proposed to combine a large-scale protein language model with the superior geometric learning capability of AlphaFold2. Our proposed method, HelixFold-Single, first pre-trains a large-scale protein language model (PLM) with thousands of millions of primary sequences utilizing the self-supervised learning paradigm, which will be used as an alternative to MSAs for learning the co-evolution information. Then, by combining the pre-trained PLM and the essential components of AlphaFold2, we obtain an end-to-end differentiable model to predict the 3D coordinates of atoms from only the primary sequence. HelixFold-Single is validated in datasets CASP14 and CAMEO, achieving competitive accuracy with the MSA-based methods on the targets with large homologous families. Furthermore, HelixFold-Single consumes much less time than the mainstream pipelines for protein structure prediction, demonstrating its potential in tasks requiring many predictions. The code of HelixFold-Single is available at https://github.com/PaddlePaddle/PaddleHelix/tree/dev/apps/protein_folding/helixfold-single, and we also provide stable web services on https://paddlehelix.baidu.com/app/drug/protein-single/forecast

Effects of habitat fragmentation and human disturbance on the population dynamics of the Yunnan snub-nosed monkey from 1994 to 2016

In this study, we integrate data from field investigations, spatial analysis, genetic analysis, and Generalized Linear Models (GLMs) to evaluate the effects of habitat fragmentation on the population dynamics, genetic diversity, and range shifts in the endangered Yunnan snub-nosed monkey (Rhinopithecus bieti). The results indicate that from 1994 to 2016, R. bieti population size increased from less than 2,000 to approximately 3,000 individuals. A primary factor promoting population recovery was the establishment of protected nature reserves. We also found that subpopulation growth rates were uneven, with the groups in some areas, and the formation of new groups. Both the fragmentation index, defined as the ratio of the number of forest patches to the total area of forest patches (e.g., increased fragmentation), and increasing human population size had a negative effect on population growth in R. bieti. We recommend that government conservation plans prioritize the protection of particular R. bieti populations, such as the Baimei and Jisichang populations, which have uncommon haplotypes. In addition, effective conservation strategies need to include an expansion of migration corridors to enable individuals from larger populations such as Guyoulong (Guilong) to serve as a source population to increase the genetic diversity of smaller R. bieti subpopulations. We argue that policies designed to protect endangered primates should not focus solely on total population size but also need to determine the amount of genetic diversity present across different subpopulations and use this information as a measure of the effectiveness of current conservation policies and the basis for new conservation policies

Global Infectious Diseases in August of 2022: Monthly Analysis

Infectious diseases have greatly affected the development of human history, owing to their unpredictable zoonotic characteristics. The recording of infectious diseases epidemic data provides information on disease transmission trends, and enables research on the risk of penitential epidemics and the mechanisms of transmission of infectious diseases. Recent years have seen a significant increase in the number of confirmed and fatal cases of COVID-19 since it became a pandemic in late 2019. Monkeypox also has potential for global transmission, because the World Health Organization (WHO) [ 1 ] reported cases of MPXV in at least 12 Countries that are not endemic for monkeypox virus. Africa and Southeast Asia appear to be the main regions where mosquito-borne diseases are epidemic, possibly because of the rainy weather in these regions in the past month. Tracking disease incidence and epidemic tendency remains imperative in these areas, although most infectious diseases appear to be dispersed and transmitted in only several areas at the moment

Global Infectious Diseases in September 2022: Monthly Analysis

The threat of infectious diseases caused by pathogenic microorganisms to both human health and the economy is enormous. Coronavirus Disease 2019 (COVID-19) remains a global pandemic. In contrast to many other infectious diseases, monkeypox spreads rapidly and cannot be ignored. Collection of data on contagious diseases can provide quantitative evidence to support effective pandemic control strategies. Global data on predominant infectious diseases collected in the past several weeks and a summary of their epidemiology are presented herein

Female Resistance to Invading Males Increases Infanticide in Langurs

BACKGROUND: Infanticide by adult male occurs in many mammalian species under natural conditions, and it is often assumed to be a goal-directed action and explained predominately by sexual selection. Motivation of this behavior in mammals is limitedly involved. METHODOLOGY AND PRINCIPAL FINDINGS: We used long-term reproductive records and direct observation in captivity and in the field of two snub-nosed langur species on the basis of individual identification to investigate how infanticide happened and to be avoided in nonhuman primates. Our observations suggested that infanticide by invading males might be more accidental than goal-directed. The invading male seemed to monopolize all the females including lactating mothers during takeovers. Multiparous mothers who accepted the invading male shortly after takeovers avoided infanticide in most cases. Our results conjectured primiparous mothers would decrease infanticidal possibility if they sexually accepted the invading male during or immediately after takeovers. In the studied langur species, voluntary abortion or mating with the invading male was evidently adopted by females to limit or avoid infanticide by takeover males. CONCLUSIONS AND SIGNIFICANCE: The objective of the invading male was to monopolize all adult females after his takeover. It appeared that the mother's resistance to accepting the new male as a mating partner was the primary incentive for infanticide. Motivation analysis might be helpful to further understand why infanticide occurs in primate species