Mbd3, a Component of NuRD/Mi-2 Complex, Helps Maintain Pluripotency of Mouse Embryonic Stem Cells by Repressing Trophectoderm Differentiation

Embryonic stem cells (ES cells) can differentiate into cells derived from all three germ layers and extraembryonic tissues. While transcription factors such as, Oct4 and Nanog are well known for their requirements for undifferentiated ES cell growth, mechanisms of epigenetic repression of germ layer specific differentiation in ES cells are not well understood. Here, we investigate functions of Mbd3, a component of nucleosome remodeling and histone deacetylation complex (NuRD/Mi-2) in mouse ES cells. We find that compared to wild type ES cells, Mbd3 knockdown cells show elevated RNA expression of trophectoderm markers, including Cdx2, Eomesodermin, and Hand1. In parallel, these cells show an increased acetylation level of histone 3 in promoters of the respective genes, suggesting Mbd3 plays a role in repression of these genes in undifferentiated ES cells. However, these changes are not sufficient for definitive differentiation to trophectoderm (TE) in chimeric embryos. When further cultured in ES medium without LIF or in trophoblast stem (TS) cell medium, Mbd3 knockdown cells differentiate into TE cells, which express Cdx2 and, at later stages, trophoblast lineage specific marker Cadherin 3. These results suggest that Mbd3 helps restrict ES cells from differentiating towards the trophectoderm lineage and is an important epigenetic player in maintaining full pluripotency of mouse ES cells

Variable Selection and Parameter Estimation with the Atan Regularization Method

Variable selection is fundamental to high-dimensional statistical modeling. Many variable selection techniques may be implemented by penalized least squares using various penalty functions. In this paper, an arctangent type penalty which very closely resembles l0 penalty is proposed; we call it Atan penalty. The Atan-penalized least squares procedure is shown to consistently select the correct model and is asymptotically normal, provided the number of variables grows slower than the number of observations. The Atan procedure is efficiently implemented using an iteratively reweighted Lasso algorithm. Simulation results and data example show that the Atan procedure with BIC-type criterion performs very well in a variety of settings

Corrosion Behavior of Alloy C-276 in Supercritical Water

The corrosion behavior of Alloy C-276 in high-temperature and high-pressure water at 500°C and 25 MPa, respectively, was investigated by means of mass gain, scanning electron microscopic observation, and X-ray diffraction. The results indicated that the mass gain rate of Alloy C-276 in supercritical water obeys the parabolic law. The oxide scale was formed on Alloy C-276 with a dual-layer structure, mainly consisting of an outer Ni-rich layer and an inner Cr2O3/NiCr2O4 mixed layer. Tiny microcracks can also be found in the oxide scale if exposed for longer time. Meanwhile, higher temperature promotes oxide rate and results in thermal stress in the oxide film

P3^3OVD: Fine-grained Visual-Text Prompt-Driven Self-Training for Open-Vocabulary Object Detection

Inspired by the success of visual-language methods (VLMs) in zero-shot classification, recent works attempt to extend this line of work into object detection by leveraging the localization ability of pre-trained VLMs and generating pseudo labels for unseen classes in a self-training manner. However, since the current VLMs are usually pre-trained with aligning sentence embedding with global image embedding, the direct use of them lacks fine-grained alignment for object instances, which is the core of detection. In this paper, we propose a simple but effective Pretrain-adaPt-Pseudo labeling paradigm for Open-Vocabulary Detection (P$^3$OVD) that introduces a fine-grained visual-text prompt adapting stage to enhance the current self-training paradigm with a more powerful fine-grained alignment. During the adapting stage, we enable VLM to obtain fine-grained alignment by using learnable text prompts to resolve an auxiliary dense pixel-wise prediction task. Furthermore, we propose a visual prompt module to provide the prior task information (i.e., the categories need to be predicted) for the vision branch to better adapt the pretrained VLM to the downstream tasks. Experiments show that our method achieves the state-of-the-art performance for open-vocabulary object detection, e.g., 31.5% mAP on unseen classes of COCO

Retention of Supraspinal Delta-like Analgesia and Loss of Morphine Tolerance in δ Opioid Receptor Knockout Mice

AbstractGene targeting was used to delete exon 2 of mouse DOR-1, which encodes the δ opioid receptor. Essentially all 3H-[D-Pen2,D-Pen5]enkephalin (3H-DPDPE) and 3H-[D-Ala2,D-Glu4]deltorphin (3H-deltorphin-2) binding is absent from mutant mice, demonstrating that DOR-1 encodes both δ1 and δ2 receptor subtypes. Homozygous mutant mice display markedly reduced spinal δ analgesia, but peptide δ agonists retain supraspinal analgesic potency that is only partially antagonized by naltrindole. Retained DPDPE analgesia is also demonstrated upon formalin testing, while the nonpeptide δ agonist BW373U69 exhibits enhanced activity in DOR-1 mutant mice. Together, these findings suggest the existence of a second delta-like analgesic system. FinallyDOR-1 mutant mice do not develop analgesic tolerance to morphine, genetically demonstrating a central role for DOR-1 in this process

Longitudinal Gut Bacterial Colonization and Its Influencing Factors of Low Birth Weight Infants During the First 3 Months of Life

Establishment of low birth weight (LBW) infant gut microbiota may have lifelong implications for the health of individuals. However, no longitudinal cohort studies have been conducted to characterize the gut microbial profiles of LBW infants and their influencing factors. Our objective was to understand how the gut bacterial community structure of LBW and normal birth weight (NBW) infants varies across the first 3 months of life and assess the influencing factors. In this observational cohort study, gut bacterial composition was identified with sequencing of the 16S rRNA gene in fecal samples of 69 LBW infants and 65 NBW controls at 0 day, 3 days, 2 weeks, 6 weeks, and 3 months (defined as stages 1–5) after birth. Alpha-diversity of both groups displayed a decreasing trend followed by slight variations. There were significant differences on the Shannon index of the two groups at stages 1 to 3 (P = 0.041, P = 0.032, and P = 0.014, respectively). The microbiota community structure of LBW infants were significantly different from NBW infants throughout the 3 months (all P < 0.05) but not at stage 2 (P = 0.054). There was a significant increase in abundance in Firmicutes while a decrease in Proteobacteria, and at genus level the abundance of Enterococcus, Klebsiella, and Streptococcus increased while it decreased for Haemophilus in LBW group. Birth weight was the main factor explaining the observed variation at all stages, except at stage 2. Delivery mode (4.78%) and antibiotic usage (3.50%) contributed to explain the observed variation at stage 3, and pregestational BMI (4.61%) partially explained the observed variation at stage 4. In conclusion, gut microbial communities differed in NBW and LBW infants from birth to 3 months of life, and were affected by birth weight, delivery mode, antibiotic treatment, and pregestational BMI

Attenuation of Vaccinia Tian Tan Strain by Removal of Viral TC7L-TK2L and TA35R Genes

Vaccinia Tian Tan (VTT) was attenuated by deletion of the TC7L-TK2L and TA35R genes to generate MVTT3. The mutant was generated by replacing the open reading frames by a gene encoding enhanced green fluorescent protein (EGFP) flanked by loxP sites. Viruses expressing EGFP were then screened for and purified by serial plaque formation. In a second step the marker EGFP gene was removed by transfecting cells with a plasmid encoding cre recombinase and selecting for viruses that had lost the EGFP phenotype. The MVTT3 mutant was shown to be avirulent and immunogenic. These results support the conclusion that TC7L-TK2L and TA35R deletion mutants can be used as safe viral vectors or as platform for vaccines