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Metastasis is a major obstacle in the therapeutic intervention of melanoma, and several GTP-binding proteins were found to play important roles in regulating cancer metastasis. To assess systematically the regulatory roles of these proteins in melanoma metastasis, we employed a targeted chemoproteomic method, which relies on the application of stable isotope-labeled desthiobiotin-GTP acyl phosphate probes in conjunction with scheduled multiple-reaction monitoring (MRM), for profiling quantitatively the GTP-binding proteins. Following probe labeling, tryptic digestion, and affinity pull-down of desthiobiotin-conjugated peptides, differences in expression levels of GTP-binding proteins in two matched pairs of primary/metastatic melanoma cell lines were measured using liquid chromatography-MRM analysis. We also showed that among the top upregulated proteins in metastatic melanoma cells, AK4 promotes the migration and invasion of melanoma cells; overexpression of AK4 in primary melanoma cells leads to augmented migration and invasion, and reciprocally, knockdown of AK4 in metastatic melanoma cells results in repressed invasiveness. In summary, we examined the relative expression levels of GTP-binding proteins in two pairs of primary/metastatic melanoma cell lines. Our results confirmed some previously reported regulators of melanoma metastasis and revealed a potential role of AK4 in promoting melanoma metastasis.

Radiotherapy constitutes a major therapeutic modality for early management of breast cancer. Despite the high efficacy in treating breast cancer (BC), radiation resistance and tumor recurrence are major hurdles in breast cancer radiotherapy. Herein, stable isotope labeling by amino acids in cell culture (SILAC) was employed, along with the parallel-reaction monitoring (PRM)-based targeted quantitative proteomic method, to examine the differences in kinase protein expression in MCF-7 and MDA-MB-231 breast cancer cells and their corresponding radioresistant C6 and C5 clones. We quantified the relative protein expression levels of 300 and 281 kinases in C5/MDA-MB-231 and C6/MCF-7 pairs of breast cancer cells, respectively. We also showed that TAF9, which was one of the differentially expressed kinases, enhances radiation resistance in breast cancer cells. Moreover, a correlation analysis of gene expression suggested TAF9s role in upregulating the expression of genes involved with radioresistance. Overall, our study uncovered a large number of differentially expressed kinases accompanied with the acquisition of radioresistance and revealed a role of TAF9 in promoting radioresistance in breast cancer.

Protein α-N-methylation is an evolutionarily conserved type of post-translational modification; however, little is known about the regulatory mechanisms for this modification. Methylation at the N6 position of adenosine in mRNAs is dynamic and modulates their stability, splicing, and translational efficiency. Here, we found that the expression of N-terminal methyltransferase 1 (NTMT1) protein is altered by depletion of those genes encoding the reader/writer/eraser proteins of N6-methyladenosine (m6A). We also observed that MRG15 is N-terminally methylated by NTMT1, and this methylation could also be modulated by reader/writer/eraser proteins of m6A. Together, these results revealed a novel m6A-based epitranscriptomic mechanism in regulating protein N-terminal methylation.

Background: Paediatric distal forearm fractures are a common ED presentation. They can be diagnosed with point-of-care ultrasound (POCUS) as an alternative to X-rays. Given that ED nurse practitioners (NPs) are relied on for the diagnosis of paediatric fractures, it is important to describe the diagnostic accuracy of NP-conducted POCUS versus X-ray.Methods: This prospective diagnostic study was conducted in a tertiary paediatric hospital in Queensland, Australia, between February 2018 and April 2019. Participants were children aged 4-16 years with a clinically non-angulated, suspected distal forearm fracture. Diagnosis from 6-view NP-administered POCUS of the distal radius and ulna was compared against the reference standard of 2-view X-ray. Each patient received both imaging modalities. Overall forearm diagnosis was classified as 'no', 'buckle' or 'other' fracture for both modalities. The primary outcome was diagnostic accuracy for 'any' fracture ('buckle' and 'other' fractures combined). Secondary outcomes included diagnostic accuracy for 'other' fractures versus 'buckle' and 'no' fractures combined, and pain, imaging duration and preference for modality.Results: Of 204 recruited patients, 129 had X-ray-diagnosed forearm fractures. The sensitivity and specificity for NP-administered POCUS were 94.6% (95% CI 89.2% to 97.3%) and 85.3% (95% CI 75.6% to 91.6%), respectively. 'Other' fractures (mostly cortical breach fractures), when compared with 'buckle'/ 'no' fractures, had sensitivity 81.0% (95% CI 69.1% to 89.1%) and specificity 95.9% (95% CI 91.3% to 98.1%). Pain and imaging duration were clinically similar between modalities. There was a preference for POCUS by patients, parents and NPs.Conclusions: NP-administered POCUS had clinically acceptable diagnostic accuracy for paediatric patients presenting with non-angulated distal forearm injuries. This included good sensitivity for diagnosis of 'any' fracture and good specificity for diagnosis of cortical breach fractures alone. Given the preference for POCUS, and the lack of difference in pain and duration between modalities, future research should consider functional outcomes comparing POCUS with X-ray in this population in a randomised controlled trial. [ABSTRACT FROM AUTHOR]

The intersection of bibliographic control and information behavior is explored in 237 issues of CCQ literature published from 1980–2023 using a combination of expanded searches within three prominent journal databases and frequency analysis of the terms "user", "seek", and "behavior" in the approximately 2,391 published items. The database searches, while inconsistent, produced a set of 43 articles (approx. 2%). Frequency and mention rates analysis using Voyant provided unique insight into both high and low occurrences of the terms. Cross-referencing both data sets produced a set of 37 volumes/issues with two prominent clusters between the years of 2009 and 2017. [ABSTRACT FROM AUTHOR]

This paper discusses Qing China's interaction with Southeast Asia in the context of border enforcement, that is, the control of movement, and expression of sovereignty. It employs both the imperial logic and the commoners' daily logic to consider how these three topics interacted with each other in the eighteenth century. I argue that the Qing court considered these issues not in terms of population, territory, or maritime prohibition, but from a standpoint of security and stability, around which the border concerns, ways of controlling people, and sovereignty were all organized. For commoners, simply making a living was the primary concern and the court's overseas activities had little to do with identity, or an anachronistic concept of sovereignty. The Qing court forbade journeys to Luzon and Batavia, the "barbarian countries" dominated by Spanish and Dutch colonial powers, but intentionally left the door open for commoners to travel to Vietnam. However, when those Chinese people stirred up trouble in Vietnam and returned to the maritime border of China, the Qing government quickly intervened. It had its own logic for enforcing domestic sovereignty and controlling the migration of people between countries. [ABSTRACT FROM AUTHOR]

CHEST would like to thank the individuals listed below, who served as reviewers for the journal in 2019. Without their generous assistance, the journal would not be able to function. The expert evaluation of manuscripts by these people is a primary reason that CHEST is one of the most respected journals in its field, and we extend our appreciation. Michael Peters Mike Shields. [Extracted from the article]

In a paper presented to the American Historical Association annual meeting in 1934, entitled "The Predicament of History," Eugen Rosenstock-Huessy (1888–1973) argued that professional (or "scientific") historians had lost touch with collective memory and were engaged in a free-floating enterprise connected to the vital past only arbitrarily or randomly. Historians should be the physicians of memory, he said. His admonitions relate closely to the stress, often discussed today, between popular heritage, or tradition and memory, on the one side, and critical history, on the other, each vying for influence and authority. Beyond his 1934 paper, Rosenstock-Huessy's grammatical method opens the way for complementarity and balance, rather than antagonism, between the popular voice and critical history. [ABSTRACT FROM AUTHOR]

This article examines the Czech writer Petra Hůlová' s representation of Mongolian women in All This Belongs to Me in an effort to discuss possible epistemological dangers involved in such cross-cultural representation of Asia by a european writing self. Through a close reading of the text, the paper explores how the represented five Mongolian females from one family are invariably subsumed under the strong patriarchal ideology of their Mongolian society. This representation of Mongolian women's oppression is then discussed in the historical context of orientalism, which has excessively exaggerated patriarchal culture of Asia and Asian women's oppression. Examining strategies Hůlová adopts to resist mere exoticization of Mongolian culture, the paper considers whether Hůlová' s cross-cultural representation presents chances for opportunities for readers outside of Mongolia to expand the horizon of their eurocentric world view. [ABSTRACT FROM AUTHOR]