Isolation and Characterization of Cross-Neutralizing Human Anti-V3 Single-Chain Variable Fragments (scFvs) Against HIV-1 from an Antigen Preselected Phage Library

Applied Biochemistry and Biotechnology - Recently conducted human phase- I trials showed protective effect of anti-HIV-1 broadly neutralizing antibodies (bnAbs). The V3 region of the HIV-1 envelope...     

Organomediated Enantioselective 18F Fluorination for PET Applications

The first organomediated asymmetric ¹⁸F fluorination has been accomplished using a chiral imidazolidinone and [¹⁸F]N‐fluorobenzenesulfonimide. The method provides access to enantioenriched ¹⁸F‐labeled α‐fluoroaldehydes (>90 % ee), which are versatile chiral ¹⁸F synthons for the synthesis of radiotracers. The utility of this process is demonstrated with the synthesis of the PET (positron emission tomography) tracer (2S,4S)‐4‐[¹⁸F]fluoroglutamic acid.     

Evaluation of muscle degeneration in inherited muscular dystrophy by nuclear magnetic resonance techniques

Nuclear magnetic resonance (NMR) techniques were applied to study the muscular dystrophy in chicks. The water proton spin-lattice relaxation times (T₁) of fast, slow, and mixed muscles and plasma were measured. The T₁ values of dystrophic pectoralis major and posterior latissimus dorsi (PLD) were significantly higher than those of the normal pectoralis and PLD muscles. The present results establish a direct relationship between the differences in T₁ values and the severity of muscle degeneration. Consistent with this conclusion, it was also found that the T₁ values of muscles unaffected in muscular dystrophy, namely, the gastrocnemius, and anterior latissimus dorsi (ALD), were not different between the normal and dystrophic chicks. Although the affected muscles of dystrophic chicks contained higher percent water and fat than those of normal chicks, the results show that the higher T₁ values is dystrophic muscles were not solely due to variations in their water content. The increase in the T₁ values is principally a result of altered interaction between cellular water and macromolecules in the diseased muscles. These data also point out the potential use of NMR imaging in evaluating muscle degeneration.     

Rapid Aqueous Late‐Stage Radiolabelling of [GaF3(BnMe2‐tacn)] by 18F/19F Isotopic Exchange: Towards New PET Imaging Probes

A simple and rapid method for ¹⁸F radiolabelling of [GaF₃(BnMe₂‐tacn)] by ¹⁸F/¹⁹F isotopic exchange is described. The use of MeCN/H₂O or EtOH/H₂O (75:25) and aqueous [¹⁸F]F^? (up to 200 MBq) with heating (80 °C, 10 min) gave 66±4 % ¹⁸F incorporation at a concentration of 268 nm , and 37±5 % ¹⁸F incorporation at even lower concentration (27 nm ), without the need for a Lewis acid promoter. A solid‐phase extraction method was established to give [Ga¹⁸F¹⁹F₂(BnMe₂‐tacn)] in 99 % radiochemical purity in an EtOH/H₂O mixture.     

Proton magnetic resonance spectroscopy and biochemical investigation of type 2 diabetes mellitus in Asian Indians: observation of high muscle lipids and C-reactive protein levels

We report the determination of intramyocellular lipids (IMCLs) of the soleus muscle of patients with type 2 diabetes mellitus (T2DM) using proton magnetic resonance spectroscopy. In addition, the various anthropometric and biochemical profiles of these patients were determined, including estimation of C-reactive protein (CRP), an inflammatory marker of coronary heart disease, and insulin resistance [Homeostasis Model Assessment (HOMA-IR)]. The estimated CRP level and the IMCL content in these patients were correlated with body mass index, percentage of body fat, other measures of abdominal obesity, serum lipoproteins, fasting and post-oral glucose load serum insulin levels and other surrogate markers of insulin resistance. The IMCL content (P=.04), CRP (P=.008) and insulin resistance (P=.0007) were significantly higher in T2DM patients compared to healthy controls. However, IMCL content did not correlate with values of fasting insulin, HOMA-IR or CRP in either group. These findings have strong implications of increased cardiovascular risk in Asian Indians with T2DM. The absence of relationship between CRP and IMCL needs to be explored further in a study using a large sample size.     

Gas-sensing properties of Fe2−xTixO3+γ (x = 0–1.4)

As part of a systematic study of mechanisms of response of semiconducting oxides as trace gas sensors, we have explored the behaviour of iron–titanium oxide solid solutions Fe_2−xTi_xO₃ (x = 0.1–1.4). The materials were single-phase for x = 0.1 with increasing proportions of a pseudobrookite second phase at higher degree of substitution. Unmodified, pure iron oxide does not show sensitivity to CO. A significant signal was developed for x = 0.1, that then diminished with increasing x and was lost for x = 1.4. Three effects have been deduced important for the gas response: significant surface segregation of Ti at low Ti content; grain growth inhibition and agglomeration into more massive, non-porous lumps as Ti content increased; and the appearance of a band-gap state associated with Fe(II) at higher Ti content. The effects of microstructure change have been analyzed by fitting the data to a simple 2-resistor model of gas-insensitive ‘grains’ in series with gas-sensitive ‘grain boundaries’. A Mars–van Krevelen type model for the response is presented, based on reactions at surface-segregated defect clusters, to develop and remove electrically-active surface trap states.     

An Activity‐Based Probe for Studying Crosslinking in Live Bacteria

Penicillin‐binding proteins (PBPs) catalyze the crosslinking of peptidoglycan (PG), an essential process for bacterial growth and survival, and a common antibiotic target. Yet, despite its importance, little is known about the spatiotemporal aspects of crosslinking—largely because of a lack of experimental tools for studying the reaction in live bacteria. Here we introduce such a tool: an activity‐based probe that enables visualization and relative quantitation of crosslinking in vivo. In Staphylococcus aureus, we show that fluorescent mimics of the natural substrate of PBPs (PG stem peptide) are covalently incorporated into the cell wall, installing fluorophores in place of natural crosslinks. These fluorescent stem peptide mimics (FSPMs) are selectively recognized by a single PBP in S. aureus: PBP4. Thus, we were able to use FSPM pulse‐labeling to localize PBP4 activity in live cells, showing that it is recruited to the septum in a manner dependent on wall teichoic acid.