Deep eutectic solvents (DESs) are an emerging class of mixtures characterized by significant depressions in melting points compared to those of the neat constituent components. These materials are ...promising for applications as inexpensive “designer” solvents exhibiting a host of tunable physicochemical properties. A detailed review of the current literature reveals the lack of predictive understanding of the microscopic mechanisms that govern the structure–property relationships in this class of solvents. Complex hydrogen bonding is postulated as the root cause of their melting point depressions and physicochemical properties; to understand these hydrogen bonded networks, it is imperative to study these systems as dynamic entities using both simulations and experiments. This review emphasizes recent research efforts in order to elucidate the next steps needed to develop a fundamental framework needed for a deeper understanding of DESs. It covers recent developments in DES research, frames outstanding scientific questions, and identifies promising research thrusts aligned with the advancement of the field toward predictive models and fundamental understanding of these solvents.
Abstract
Adipose tissue is present in close proximity to various organs in the human body. One prominent example is fat contained in the mesentery that is contiguous with all abdominal digestive ...organs including the intestine. Despite the fact that mesenteric fat-wrapping around the inflamed gut (so called “creeping fat”) was described as a characteristic feature of Crohn’s disease (CD) in the early 1930s, the functional implications of creeping fat have received only recent attention. As a potent producer of fatty acids, cytokines, growth factors, and adipokines, creeping fat plays an important role in regulation of immunity and inflammation. Increasing evidence points to a link between creeping fat and intestinal inflammation in CD, where histopathologic evaluation shows a significant association between creeping fat and connective tissue changes in the bowel wall, such as muscular hypertrophy, fibrosis, and stricture formation. In addition, emerging mechanistic data indicate a link between creeping fat, muscularis propria hyperplasia, and stricturing disease. Information on fat–mesenchymal interactions in other organs could provide clues to fill the fundamental knowledge gap on the role of distinct components of creeping fat in intestinal fibrosis and stricture formation. Future studies will provide important new information that in turn could lead to novel therapeutic agents aimed at prevention or treatment of CD-associated fibrosis and stricture formation.
The maleimide motif is widely used for the selective chemical modification of cysteine residues in proteins. Despite widespread utilization, there are some potential limitations, including the ...irreversible nature of the reaction and, hence, the modification and the number of attachment positions. We conceived of a new class of maleimide which would address some of these limitations and provide new opportunities for protein modification. We report herein the use of mono- and dibromomaleimides for reversible cysteine modification and illustrate this on the SH2 domain of the Grb2 adaptor protein (L111C). After initial modification of a protein with a bromo- or dibromomaleimide, it is possible to add an equivalent of a second thiol to give further bioconjugation, demonstrating that bromomaleimides offer opportunities for up to three points of attachment. The resultant protein−maleimide products can be cleaved to regenerate the unmodified protein by addition of a phosphine or a large excess of a thiol. Furthermore, dibromomaleimide can insert into a disulfide bond, forming a maleimide bridge, and this is illustrated on the peptide hormone somatostatin. Fluorescein-labeled dibromomaleimide is synthesized and inserted into the disulfide to construct a fluorescent somatostatin analogue. These results highlight the significant potential for this new class of reagents in protein modification.
Little is known about the active positioning of transcripts outside of embryogenesis or highly polarized cells. We show here that a specific G1 cyclin transcript is highly clustered in the cytoplasm ...of large multinucleate cells. This heterogeneous cyclin transcript localization results from aggregation of an RNA-binding protein, and deletion of a polyglutamine stretch in this protein results in random transcript localization. These multinucleate cells are remarkable in that nuclei cycle asynchronously despite sharing a common cytoplasm. Notably, randomization of cyclin transcript localization significantly diminishes nucleus-to-nucleus differences in the number of mRNAs and synchronizes cell-cycle timing. Thus, nonrandom cyclin transcript localization is important for cell-cycle timing control and arises due to polyQ-dependent behavior of an RNA-binding protein. There is a widespread association between polyQ expansions and RNA-binding motifs, suggesting that this is a broadly exploited mechanism to produce spatially variable transcripts and heterogeneous cell behaviors.
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•Whi3 RNA-binding proteins cluster CLN3 transcripts to pattern the Ashbya syncytium•Cyclin transcript clustering requires a polyQ region in Whi3•Local differences in cyclin transcript clustering control nuclear cell-cycle times•Thus, polyQ clustering of RNA-binding proteins can spatially pattern mRNA function
Lee et al. demonstrate that a G1-cyclin transcript is highly clustered in the cytoplasm of large multinucleate Ashbya cells. Heterogeneous transcript localization results from polyQ-mediated aggregation of an RNA-binding protein. Nonrandom cyclin transcript localization controls local nuclear cell-cycle timing and promotes asynchronous cycling of nuclei in a common cytoplasm.
Urban domestic cat (Felis catus) populations can attain exceedingly high densities and are not limited by natural prey availability. This has generated concerns that they may negatively affect prey ...populations, leading to calls for management. We enlisted cat-owners to record prey returned home to estimate patterns of predation by free-roaming pets in different localities within the town of Reading, UK and questionnaire surveys were used to quantify attitudes to different possible management strategies. Prey return rates were highly variable: only 20% of cats returned ≥4 dead prey annually. Consequently, approximately 65% of owners received no prey in a given season, but this declined to 22% after eight seasons. The estimated mean predation rate was 18.3 prey cat⁻¹ year⁻¹ but this varied markedly both spatially and temporally: per capita predation rates declined with increasing cat density. Comparisons with estimates of the density of six common bird prey species indicated that cats killed numbers equivalent to adult density on c. 39% of occasions. Population modeling studies suggest that such predation rates could significantly reduce the size of local bird populations for common urban species. Conversely, most urban residents did not consider cat predation to be a significant problem. Collar-mounted anti-predation devices were the only management action acceptable to the majority of urban residents (65%), but were less acceptable to cat-owners because of perceived risks to their pets; only 24% of cats were fitted with such devices. Overall, cat predation did appear to be of sufficient magnitude to affect some prey populations, although further investigation of some key aspects of cat predation is warranted. Management of the predation behavior of urban cat populations in the UK is likely to be challenging and achieving this would require considerable engagement with cat owners.
The ACR Incidental Findings Committee (IFC) presents recommendations for managing pancreatic cysts that are incidentally detected on CT or MRI. These recommendations represent an update from the ...pancreatic component of the JACR 2010 white paper on managing incidental findings in the adrenal glands, kidneys, liver, and pancreas. The Pancreas Subcommittee-which included abdominal radiologists, a gastroenterologist, and a pancreatic surgeon-developed this algorithm. The recommendations draw from published evidence and expert opinion, and were finalized by informal iterative consensus. Algorithm branches successively categorize pancreatic cysts based on patient characteristics and imaging features. They terminate with an ascertainment of benignity and/or indolence (sufficient to discontinue follow-up), or a management recommendation. The algorithm addresses most, but not all, pathologies and clinical scenarios. Our goal is to improve quality of care by providing guidance on how to manage incidentally detected pancreatic cysts.
No reliable method for evaluating intestinal fibrosis in Crohn’s disease (CD) exists; therefore, we developed a computed-tomography enterography (CTE)–based radiomic model (RM) for characterizing ...intestinal fibrosis in CD.
This retrospective multicenter study included 167 CD patients with 212 bowel lesions (training, 98 lesions; test, 114 lesions) who underwent preoperative CTE and bowel resection at 1 of the 3 tertiary referral centers from January 2014 through June 2020. Bowel fibrosis was histologically classified as none–mild or moderate–severe. In the training cohort, 1454 radiomic features were extracted from venous-phase CTE and a machine learning–based RM was developed based on the reproducible features using logistic regression. The RM was validated in an independent external test cohort recruited from 3 centers. The diagnostic performance of RM was compared with 2 radiologists’ visual interpretation of CTE using receiver operating characteristic (ROC) curve analysis.
In the training cohort, the area under the ROC curve (AUC) of RM for distinguishing moderate–severe from none–mild intestinal fibrosis was 0.888 (95% confidence interval CI, 0.818–0.957). In the test cohort, the RM showed robust performance across 3 centers with an AUC of 0.816 (95% CI, 0.706–0.926), 0.724 (95% CI, 0.526–0.923), and 0.750 (95% CI, 0.560–0.940), respectively. Moreover, the RM was more accurate than visual interpretations by either radiologist (radiologist 1, AUC = 0.554; radiologist 2, AUC = 0.598; both, P < .001) in the test cohort. Decision curve analysis showed that the RM provided a better net benefit to predicting intestinal fibrosis than the radiologists.
A CTE-based RM allows for accurate characterization of intestinal fibrosis in CD.
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