Impact of Intrinsic Muscle Weakness on Muscle–Bone Crosstalk in Osteogenesis Imperfecta

Bone and muscle are highly synergistic tissues that communicate extensively via mechanotransduction and biochemical signaling. Osteogenesis imperfecta (OI) is a heritable connective tissue disorder of severe bone fragility and recently recognized skeletal muscle weakness. The presence of impaired bone and muscle in OI leads to a continuous cycle of altered muscle–bone crosstalk with weak muscles further compromising bone and vice versa. Currently, there is no cure for OI and understanding the pathogenesis of the skeletal muscle weakness in relation to the bone pathogenesis of OI in light of the critical role of muscle–bone crosstalk is essential to developing and identifying novel therapeutic targets and strategies for OI. This review will highlight how impaired skeletal muscle function contributes to the pathophysiology of OI and how this phenomenon further perpetuates bone fragility.     

GOLPH3 Regulates EGFR in T98G Glioblastoma Cells by Modulating Its Glycosylation and Ubiquitylation

Protein trafficking is altered when normal cells acquire a tumor phenotype. A key subcellular compartment in regulating protein trafficking is the Golgi apparatus, but its role in carcinogenesis is still not well defined. Golgi phosphoprotein 3 (GOLPH3), a peripheral membrane protein mostly localized at the trans-Golgi network, is overexpressed in several tumor types including glioblastoma multiforme (GBM), the most lethal primary brain tumor. Moreover, GOLPH3 is currently considered an oncoprotein, however its precise function in GBM is not fully understood. Here, we analyzed in T98G cells of GBM, which express high levels of epidermal growth factor receptor (EGFR), the effect of stable RNAi-mediated knockdown of GOLPH3. We found that silencing GOLPH3 caused a significant reduction in the proliferation of T98G cells and an unexpected increase in total EGFR levels, even at the cell surface, which was however less prone to ligand-induced autophosphorylation. Furthermore, silencing GOLPH3 decreased EGFR sialylation and fucosylation, which correlated with delayed ligand-induced EGFR downregulation and its accumulation at endo-lysosomal compartments. Finally, we found that EGF failed at promoting EGFR ubiquitylation when the levels of GOLPH3 were reduced. Altogether, our results show that GOLPH3 in T98G cells regulates the endocytic trafficking and activation of EGFR likely by affecting its extent of glycosylation and ubiquitylation.     

Proteome profiling of exosomes derived from plasma of heifers with divergent genetic merit for fertility

The current study evaluated exosomes isolated from plasma of heifers bred to have high or low fertility through developing extreme diversity in fertility breeding values, however, key animal traits (e.g., body weight, milk production, and percentage of North American genetics) remained similar between the 2 groups. The exosomes were isolated by a combined ultracentrifugation and size exclusion chromatography approach and characterized by their size distribution (nanoparticle tracking analysis), morphology (transmission electron microscopy), and presence of exosomal markers (immunoblotting). In addition, a targeted mass spectrometry approach was used to confirm the presence of 2 exosomal markers, tumor susceptibility gene 101 and flotillin 1. The number of exosomes from plasma of high fertility heifers was greater compared with low fertility heifers. Interestingly, the exosomal proteomic profile, evaluated using mass spectrometry, identified 89 and 116 proteins in the high and low fertility heifers respectively, of which 4 and 31 were unique, respectively. These include proteins associated with specific biological processes and molecular functions of fertility. Most notably, the tetratricopeptide repeat protein 41-related, glycodelin, and kelch-like protein 8 were identified in plasma exosomes unique to the low fertility heifers. These proteins are suggested to play a role in reproduction; however, the role of these proteins in dairy cow reproduction remains to be elucidated. Their identification underscores the potential for proteins within exosomes to provide information on the fertility status and physiological condition of the cow. This may potentially lead to the development of prognostic tools and interventions to improving dairy cow fertility.     

Physical filtration efficiency analysis of a polyaniline hybrid composite filter with graphite oxide for particulate matter 2.5

Particulate matter (PM) 2.5 pollution is a prevalent environmental and public health issue that has raised serious global concerns. Because standard heating, ventilation, and air conditioning filters are incapable of filtering out PM 2.5 particles efficiently, different methods of PM 2.5 filtration, such as physical filtration and electrostatic filtration, are under investigation to develop a filter with a high filtration efficiency and a low pressure drop. According to various studies, pressure drop has a significant influence on the filtration efficiency. An equation for the theoretical trend was generated based on the composite data gathered from similar filtration studies and was used to evaluate the relationship between pressure drop and filtration efficiency. Here, the theoretical equation indicated that the filtration efficiency increased as the pressure drop on a filter increased until 0.01 psi where the efficiency remained near constant at approximately 99.9%. In this study, we introduce a graphite oxide (GO) and polyaniline (PANi) composite hybrid filter in order to create a low-pressure (1.2 psi) drop filter. By adding GO flakes to the PANi matrix, we not only produced a highly permeable filter while allowing continuous gas flow, but also achieved a remarkable and highly effective PM 2.5 filter with a filtration efficiency of 99.7 ± 0.08%.     

Understanding the Self-Assembly of Cellulose Nanocrystals—Toward Chiral Photonic Materials

Over millions of years, animals and plants have evolved complex molecules and structures that endow them with vibrant colors. Among the sources of natural coloration, structural color is prominent in insects, bird feathers, snake skin, plants, and other organisms, where the color arises from the interaction of light with nanoscale features rather than absorption from a pigment. Cellulose nanocrystals (CNCs) are a biorenewable resource that spontaneously organize into chiral nematic liquid crystals having a hierarchical structure that resembles the Bouligand structure of arthropod shells. The periodic, chiral nematic organization of CNC films leads them to diffract light, making them appear iridescent. Over the past two decades, there have been many advances to develop the photonic properties of CNCs for applications ranging from cosmetics to sensors. Here, the origin of color in CNCs, the control of photonic properties of CNC films, the development of new composite materials of CNCs that can yield flexible photonic structures, and the future challenges in this field are discussed. In particular, recent efforts to make flexible photonic materials using CNCs are highlighted.     

Evaluation of environmental design strategies for university buildings

ABSTRACT

This paper examines the performance of environmental strategies in seven recently constructed or refurbished university buildings in the UK. These buildings contain a range of administrative spaces, classrooms, libraries and studios, reflecting their often complex, multi-use, heterogeneous nature. The key features of each environmental strategy are described (including passive, mixed-mode or active systems), in the context of the occupants and spaces they serve and the level of interaction that they afford. Energy performance and occupant thermal comfort (assessed by user surveys) are analysed and compared with studies of other non-domestic buildings, which have typically focused on more predictable single administrative uses (e.g. government offices), and unusually effective operation scenarios (e.g. continuous monitoring by expert building managers). The paper concludes by examining two of the case studies that reflect an increasingly common model of ‘flexible’ environmental design in more detail, identifying key features of the strategies for each building that have had a significant impact on their performance. The design assumptions leading to these features will be explored, and key lessons identified, contributing towards the development of a more robust evidential basis for choosing appropriate environmental strategies for university and other non-domestic buildings in the UK.     

EEM fluorescence spectroscopy as a fast method to assess the brine composition of salted herring

Ripening of barrel-salted herring (Clupea harengus) is evaluated by the use of fluorescence spectroscopy and protein determinations. During ripening, protein degradation takes place in the herring and protein is extracted into the brine. The present study aims at identifying parameters which are correlated to the ripening characteristics of barrel-salted herring and which can provide a better understanding of the ripening process. Front face fluorescence landscapes were obtained by measuring directly on the brine from barrel-salted herring. These data were analyzed by parallel factor analysis (PARAFAC), which revealed four fluorophores, tryptophan (two states), vitamin B6 and riboflavin. All four parameters showed an increase in concentration during the storage period corresponding to an increase in protein content that varied from 3 g/100 g at day 60 to 5 g/100 g after 277 days of storage. It was not possible to see a difference in the development of the four fluorophores during the ripening period. The protein content was predicted from the fluorescence landscapes by partial least squares (PLS). The use of unfolded fluorescence spectra gave an RMSECV of 0.26 g/100 g and a correlation between the measured protein content and the predicted values of 0.86.     

Translational Read-Through Therapy of RPGR Nonsense Mutations

X-chromosomal retinitis pigmentosa (RP) frequently is caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. We evaluated the potential of PTC124 (Ataluren, Translama^TM) treatment to promote ribosomal read-through of premature termination codons (PTC) in RPGR. Expression constructs in HEK293T cells showed that the efficacy of read-through reagents is higher for UGA than UAA PTCs. We identified the novel hemizygous nonsense mutation c.1154T > A, p.Leu385* ({"type":"entrez-nucleotide","attrs":{"text":"NM_000328.3","term_id":"1677500221"}}NM_000328.3) causing a UAA PTC in RPGR and generated patient-derived fibroblasts. Immunocytochemistry of serum-starved control fibroblasts showed the RPGR protein in a dot-like expression pattern along the primary cilium. In contrast, RPGR was no longer detectable at the primary cilium in patient-derived cells. Applying PTC124 restored RPGR at the cilium in approximately 8% of patient-derived cells. RT-PCR and Western blot assays verified the pathogenic mechanisms underlying the nonsense variant. Immunofluorescence stainings confirmed the successful PTC124 treatment. Our results showed for the first time that PTC124 induces read-through of PTCs in RPGR and restores the localization of the RPGR protein at the primary cilium in patient-derived cells. These results may provide a promising new treatment option for patients suffering from nonsense mutations in RPGR or other genetic diseases.     

Utilization of different tall oils for improving the water resistance of cellulosic fibers

This study was conducted to assess the effect of the pulping by-products crude tall oil (CTO), distilled tall oil (DTO), and tall oil fatty acid (TOFA) on dynamic water vapor sorption behavior, interfiber strength, and thermal stability of cellulosic paper-sheets. The results were compared against those obtained in cellulose papers treated with the conventional petroleum-derived hydrophobic agent hydrowax and in untreated ones. The tall oil treatments caused strong reduction in equilibrium moisture content of the paper-sheets during adsorption and desorption runs. The same trend was noticed for the hydrowax-treated papers, however, it was less pronounced than the CTO-treated and DTO-treated samples in the relative humidity range of 75–95%. The sorption hysteresis was considerably decreased after the treatments. The ultimate dry-tensile strengths of the paper-sheets were significantly reduced by TOFA and hydrowax treatments, while CTO and DTO showed comparable strength as that of untreated control. The ultimate wet-strengths of the paper-sheets were improved after the treatments. The thermal stability of the specimens was improved by the tall oil treatments, and the hydrowax-treated samples illustrated lower degradation temperature than the untreated control. The results are promising for the use of tall oils as alternative hydrophobic agents of cellulosic fiber-based products, such as wood panels and paper packaging. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47303.