A Comprehensive Review of Genetically Engineered Mouse Models for Prader-Willi Syndrome Research

Prader-Willi syndrome (PWS) is a neurogenetic multifactorial disorder caused by the deletion or inactivation of paternally imprinted genes on human chromosome 15q11-q13. The affected homologous locus is on mouse chromosome 7C. The positional conservation and organization of genes including the imprinting pattern between mice and men implies similar physiological functions of this locus. Therefore, considerable efforts to recreate the pathogenesis of PWS have been accomplished in mouse models. We provide a summary of different mouse models that were generated for the analysis of PWS and discuss their impact on our current understanding of corresponding genes, their putative functions and the pathogenesis of PWS. Murine models of PWS unveiled the contribution of each affected gene to this multi-facetted disease, and also enabled the establishment of the minimal critical genomic region (PWScr) responsible for core symptoms, highlighting the importance of non-protein coding genes in the PWS locus. Although the underlying disease-causing mechanisms of PWS remain widely unresolved and existing mouse models do not fully capture the entire spectrum of the human PWS disorder, continuous improvements of genetically engineered mouse models have proven to be very powerful and valuable tools in PWS research.     

Thermal analysis of novel underfill materials with optimum processing characteristics

This work encompasses the development of low‐viscosity cyclic oligomer underfill formulations that cure without heat evolution. Boron nitride, silica‐coated aluminum nitride, and alumina ceramic powders were used as fillers in cyclic butylene terephthalate oligomer melts. The melts were heated with a suitable catalyst to induce polymerization. The effects of the filler type and composition on the thermal and mechanical properties of the poly(butylene terephthalate)/filler composites were examined with differential scanning calorimetry, temperature‐modulated differential scanning calorimetry, thermogravimetric analysis, thermomechanical analysis, and dynamic mechanical analysis. Scanning electron microscopy was employed to elucidate the morphology of these composites. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 1300–1307, 2005     

Small RNA F6 Provides Mycobacterium smegmatis Entry into Dormancy

Regulatory small non-coding RNAs play a significant role in bacterial adaptation to changing environmental conditions. Various stresses such as hypoxia and nutrient starvation cause a reduction in the metabolic activity of Mycobacterium smegmatis, leading to entry into dormancy. We investigated the functional role of F6, a small RNA of M. smegmatis, and constructed an F6 deletion strain of M. smegmatis. Using the RNA-seq approach, we demonstrated that gene expression changes that accompany F6 deletion contributed to bacterial resistance against oxidative stress. We also found that F6 directly interacted with 5′-UTR of MSMEG_4640 mRNA encoding RpfE2, a resuscitation-promoting factor, which led to the downregulation of RpfE2 expression. The F6 deletion strain was characterized by the reduced ability to enter into dormancy (non-culturability) in the potassium deficiency model compared to the wild-type strain, indicating that F6 significantly contributes to bacterial adaptation to non-optimal growth conditions.     

The New Version of the ANDDigest Tool with Improved AI-Based Short Names Recognition

The body of scientific literature continues to grow annually. Over 1.5 million abstracts of biomedical publications were added to the PubMed database in 2021. Therefore, developing cognitive systems that provide a specialized search for information in scientific publications based on subject area ontology and modern artificial intelligence methods is urgently needed. We previously developed a web-based information retrieval system, ANDDigest, designed to search and analyze information in the PubMed database using a customized domain ontology. This paper presents an improved ANDDigest version that uses fine-tuned PubMedBERT classifiers to enhance the quality of short name recognition for molecular-genetics entities in PubMed abstracts on eight biological object types: cell components, diseases, side effects, genes, proteins, pathways, drugs, and metabolites. This approach increased average short name recognition accuracy by 13%.     

Gamma Radiation Effects on the Glass Transition Temperature and Mechanical Properties of PMMA/soot nanocomposites

Summary Poly(methyl methacrylate) (PMMA) was produced via free radical polymerization. Polymer samples were sonicated and melt compounded to form 1%, 0.5%, and 0.25% PMMA/soot samples. Soot containing unpurified carbon nanotubes was provided by NASA Ames Research Center. The composites were compression molded and exposed to ionizing radiation in air from a Cesium-137 source. The PMMA/soot samples were characterized before and after exposure to radiation. Differential Scanning Calorimetry (DSC) was used to determine glass transition temperatures. Mechanical properties of composites were characterized via Dynamic Mechanical Analysis (DMA) and microhardness measurements. The glass transition temperatures from this study, when compared to similar studies conducted by Harmon et. al on purified single-wall and multi-wall carbon nanotube composites indicate that soot composites possess lower radiation resistance.     

An immersive virtual peer for studying social influences on child cyclists' road-crossing behavior

The goal of our work is to develop a programmatically controlled peer to bicycle with a human subject for the purpose of studying how social interactions influence road-crossing behavior. The peer is controlled through a combination of reactive controllers that determine the gross motion of the virtual bicycle, action-based controllers that animate the virtual bicyclist and generate verbal behaviors, and a keyboard interface that allows an experimenter to initiate the virtual bicyclist's actions during the course of an experiment. The virtual bicyclist's repertoire of behaviors includes road following, riding alongside the human rider, stopping at intersections, and crossing intersections through specified gaps in traffic. The virtual cyclist engages the human subject through gaze, gesture, and verbal interactions. We describe the structure of the behavior code and report the results of a study examining how 10- and 12-year-old children interact with a peer cyclist that makes either risky or safe choices in selecting gaps in traffic. Results of our study revealed that children who rode with a risky peer were more likely to cross intermediate-sized gaps than children who rode with a safe peer. In addition, children were significantly less likely to stop at the last six intersections after the experience of riding with the risky than the safe peer during the first six intersections. The results of the study and children's reactions to the virtual peer indicate that our virtual peer framework is a promising platform for future behavioral studies of peer influences on children's bicycle riding behavior.     

An Eleven-microRNA Signature Related to Tumor-Associated Macrophages Predicts Prognosis of Breast Cancer

The dysregulation of microRNAs (miRNAs) has been known to play important roles in tumor development and progression. However, the understanding of the involvement of miRNAs in regulating tumor-associated macrophages (TAMs) and how these TAM-related miRNAs (TRMs) modulate cancer progression is still in its infancy. This study aims to explore the prognostic value of TRMs in breast cancer via the construction of a novel TRM signature. Potential TRMs were identified from the literature, and their prognostic value was evaluated using 1063 cases in The Cancer Genome Atlas Breast Cancer database. The TRM signature was further validated in the external Gene Expression Omnibus {"type":"entrez-geo","attrs":{"text":"GSE22220","term_id":"22220"}}GSE22220 dataset. Gene sets enrichment analyses were performed to gain insight into the biological functions of this TRM signature. An eleven-TRM signature consisting of mir-21, mir-24-2, mir-125a, mir-221, mir-22, mir-501, mir-365b, mir-660, mir-146a, let-7b and mir-31 was constructed. This signature significantly differentiated the high-risk group from the low-risk in terms of overall survival (OS)/ distant-relapse free survival (DRFS) (p value < 0.001). The prognostic value of the signature was further enhanced by incorporating other independent prognostic factors in a nomogram-based prediction model, yielding the highest AUC of 0.79 (95% CI: 0.72–0.86) at 5-year OS. Enrichment analyses confirmed that the differentially expressed genes were mainly involved in immune-related pathways such as adaptive immune response, humoral immune response and Th1 and Th2 cell differentiation. This eleven-TRM signature has great potential as a prognostic factor for breast cancer patients besides unravelling the dysregulated immune pathways in high-risk breast cancer.     

Structure and electrical conductivity of nitrogen-doped carbon nanofibers

The effect of nitrogen concentration in carbon nanofibers (CNFs) on the structural and electrical properties of the carbon material was studied. CNFs with nitrogen concentration varied from 0 to 8.2 wt.% (N-CNFs) with “herringbone” structure were prepared by decomposition of ethylene and ethylene mixture with ammonia over 65Ni-25Cu-10Al₂O₃ (wt.%) catalyst at 823 K. Detailed investigation of the CNFs and N-CNFs by XPS, FTIR and Raman spectroscopy showed that the nitrogen introduction in carbon material distorts the graphite-like lattice and increases the structure defectiveness. Both effects become more significant as the nitrogen concentration in N-CNFs grows.The electrical conductivity of N-CNFs with different nitrogen concentrations is caused by the competition of the nanofiber graphite-like structure disordering after introduction of nitrogen atoms and doping of an additional electron into the delocalized π-system of the graphite-like material. As a result, the maximum electrical conductivity among the samples studied was observed at nitrogen concentration in N-CNFs equal to 3.1 wt.%.     

Synchronizing self and object movement: How child and adult cyclists intercept moving gaps in a virtual environment.

Two experiments examined how 10- and 12-year-old children and adults intercept moving gaps while bicycling in an immersive virtual environment. Participants rode an actual bicycle along a virtual roadway. At 12 test intersections, participants attempted to pass through a gap between 2 moving, car-sized blocks without stopping. The blocks were timed such that it was sometimes necessary for participants to adjust their speed in order to pass through the gap. We manipulated available visual information by presenting the target blocks in isolation in Experiment 1 and in streams of blocks in Experiment 2. In both experiments, adults had more time to spare than did children. Both groups had more time to spare when they were required to slow down than when they were required to speed up. Participants' behavior revealed a multistage interception strategy that cannot be explained by the use of a monotonic control law such as the constant bearing angle strategy. The General Discussion section focuses on possible sources of changes in perception-action coupling over development and on task-specific constraints that could underlie the observed interception strategy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)