We have prepared a series of molecular multimeric MR contrast agents for cell labeling that are easy to synthesize, relatively low molecular weight, and biocompatible. The relaxivities of the agents range from 17 to 85 mM(-1) s(-1). Cellular uptake is concentration dependent and viability is excellent. MR images of cell pellets reveal a marked increase in observed signal intensity.

The COVID-19 pandemic caused by SARS-CoV-2 is in immediate need of an effective antidote. Although the Spike glycoprotein (SgP) of SARS-CoV-2 has been shown to bind to heparins, the structural features of this interaction, the role of a plausible heparan sulfate proteoglycan (HSPG) receptor, and the antagonism of this pathway through small molecules remain unaddressed. Using an in vitro cellular assay, we demonstrate HSPGs modified by the 3-O-sulfotransferase isoform-3, but not isoform-5, preferentially increased SgP-mediated cell-to-cell fusion in comparison to control, unmodified, wild-type HSPGs. Computational studies support preferential recognition of the receptor-binding domain of SgP by 3-O-sulfated HS sequences. Competition with either fondaparinux, a 3-O-sulfated HS-binding oligopeptide, or a synthetic, non-sugar small molecule, blocked SgP-mediated cell-to-cell fusion. Finally, the synthetic, sulfated molecule inhibited fusion of GFP-tagged pseudo SARS-CoV-2 with human 293T cells with sub-micromolar potency. Overall, overexpression of 3-O-sulfated HSPGs contribute to fusion of SARS-CoV-2, which could be effectively antagonized by a synthetic, small molecule.

The pulsating bubble surfactometer (PBS) is often used for in vitro characterization of exogenous lung surfactant replacements and lung surfactant components. However, the commercially available PBS is not able to dynamically track bubble size and shape. The PBS therefore does not account for bubble growth or elliptical bubble shape that frequently occur during device use. More importantly, the oscillatory volume changes of the pulsating bubble are different than those assumed by the software of the commercial unit. This leads to errors in both surface area and surface tension measurements. We have modified a commercial PBS through the addition of an image-acquisition system, allowing real-time determination of bubble size and shape and hence the accurate tracking of surface area and surface tension. Compression-expansion loops obtained with the commercially available PBS software were compared with those provided by the image-analysis system for dipalmitoylphosphatidylcholine, Infasurf, and Tanaka lipids (dipalmitoylphosphatidylcholine-palmitoyloleoylphosphatidyl-glycerol-palmitic acid, 68:22:9) at concentrations of 0.1 and 1.0 mg/ml and at frequencies of 1 and 20 cycles/min. Whereas minimum surface tension as determined by the image-analysis system is similar to that measured by the commercially available software, the maximum surface tension and the shapes of the interfacial area-surface tension loops are quite different. Differences are attributable to bubble drift, nonsinusoidal volume changes, and variable volume excursions seen with the modified system but neglected by the original system. Image analysis reveals that the extent of loop hysteresis is greatly overestimated by the commercial device and that an apparent, rapid increase in surface tension upon film expansion seen in PBS loops is not observed with the image-analysis system. The modified PBS system reveals new dynamic characteristics of lung surfactant preparations that have not previously been reported.

). Only 5-10% of breast cancers are associated with mutations in the susceptibility genes BRCA1 and BRCA2. However, in cases associated with strong family history, mutation rates are higher, ranging from 16% to 26% for BRCA1 [1][2][3] and from 7% to 13% for BRCA2.2 3 However, many breast cancer patients with strong family histories have no obvious mutations in BRCA1/2. While there is an active search for other breast cancer susceptibility genes, it is possible that the true contributions of BRCA1 and BRCA2 to early onset breast cancer have been underestimated. Indeed, one study has shown that only 63% of breast cancer families linked to BRCA1 are associated with detectable mutations in BRCA1. 4Several reasons for this discrepancy are possible. For example, mutations in BRCA1 promoter sequences might be undetectable by current detection techniques. Additionally, inherited genomic rearrangements that inactivate BRCA1 and BRCA2 but cannot be detected by conventional polymerase chain reaction (PCR) based assays have been reported. 5-10Finally, it is possible that some genetic variants previously dismissed as ''unclassified variants'' or ''polymorphisms'' may have hitherto underappreciated effects on protein synthesis or function.Most studies of BRCA1 and BRCA2 associated breast cancers have focused on white populations, yet several observations suggest that there might be a genetic component to breast cancer susceptibility in families of African ancestry.11 Breast cancer is less common in African populations than in other populations but, when it does occur, it is characterised by an early age of onset and a higher mortality.12-14 Additionally, histopathological studies have revealed striking similarities between breast tumours that occur in BRCA1 mutation carriers and patients of African descent, including a higher likelihood of being high grade, hormone receptor negative, and showing increased S-phase and nuclear atypia. 15-21Thus it is important to know whether BRCA1 and/or BRCA2 mutations play any role in the early onset breast cancers that disproportionately affect patients of African ancestry. We previously described the first analysis of truncating BRCA1 and BRCA2 alleles in a population of Nigerian breast cancer patients aged 40 years or younger. 22 This study showed that, while protein truncating alleles are surprisingly less frequent in the Nigerian cohort than other populations studied, the total level of genetic variability in these genes was very high. In the present study, we examine whether non-truncating alleles of BRCA1 or BRCA2 are associated with breast cancers in a similar cohort. Specifically, we addressed whether BRCA1/2 sequence variations are more frequent in African breast cancer populations than in other populations; whether there is a distinctive spectrum of BRCA1/2 sequence variations in African patients that may identify functionally critical protein domains; and whether there are founder mutations that occur frequently in breast cancer populations of African descent. Key pointsN Breast ...

Despite recent advances in tissue engineering to regenerate biological function by combining cells with material supports, development is hindered by inadequate techniques for characterizing biomaterials in vivo. Magnetic resonance imaging is a tomographic technique with high temporal and spatial resolution and represents an excellent imaging modality for longitudinal noninvasive assessment of biomaterials in vivo. To distinguish biomaterials from surrounding tissues for magnetic resonance imaging, protein polymer contrast agents were developed and incorporated into hydrogels. In vitro and in vivo images of protein polymer hydrogels, with and without covalently incorporated protein polymer contrast agents, were acquired by magnetic resonance imaging. T 1 values of the labeled gels were consistently lower when protein polymer contrast agents were included. As a result, the protein polymer contrast agent hydrogels facilitated fate tracking, quantification of degradation, and detection of immune response in vivo. For the duration of the in vivo study, the protein polymer contrast agent-containing hydrogels could be distinguished from adjacent tissues and from the foreign body response surrounding the gels. The hydrogels containing protein polymer contrast agent have a contrast-to-noise ratio 2-fold greater than hydrogels without protein polymer contrast agent. In the absence of the protein polymer contrast agent, hydrogels cannot be distinguished by the end of the gel lifetime. Magn Reson Med 65:220-228, 2011. V C 2010 Wiley-Liss, Inc.