Search

Introduction: Diabetes is a common syndrome characterized by a steady rise in blood glucose levels and has various side effects, including oral complications such as periodontitis and dry mouth. Material and Methods: This case-control study was performed on 30 patients with type 2 diabetes mellitus and 30 normal people who were referred to Kowsar Hospital of Semnan, Iran. The study groups were evaluated for HbA1C, and unstimulated saliva and data were statistically analyzed. Results: Unstimulated saliva in diabetic patients was 0.02 ± 0.07 ml/min and ± 14.0 ± 02.0 ml in the control group (P <0.001). In the diabetic group, 18 out of the 30 diabetic patients (60%) had uncontrolled glucose (HbA1c was 7% or higher), and the rest had controlled glucose. According to the HbA1c study, the mean standard deviation of unstimulated saliva in controlled diabetic patients was 0.08 0 ± 0.02 ml/min and 0.06 ± 0.02 ml/min in uncontrolled patients, which showed a significant difference (p=0.006). Conclusion: Dry mouth was more prevalent in people with uncontrolled diabetes, so blood glucose level and its control had a significant effect on the reduction of unstimulated salivation. [ABSTRACT FROM AUTHOR]

The membrane proximal external region (MPER) of HIV-1 envelope glycoprotein (gp) 41 is an attractive vaccine target for elicitation of broadly neutralizing antibodies (bNAbs) by vaccination. However, current details regarding the quaternary structural organization of the MPER within the native prefusion trimer [(gp120/41)3] are elusive and even contradictory, hindering rational MPER immunogen design. To better understand the structural topology of the MPER on the lipid bilayer, the adjacent transmembrane domain (TMD) was appended (MPER-TMD) and studied. Membrane insertion of the MPER-TMD was sensitive both to the TMD sequence and cytoplasmic residues. Antigen binding of MPER-specific bNAbs, in particular 10E8 and DH511.2_K3, was significantly impacted by the presence of the TMD. Furthermore, MPER-TMD assembly into 10-nm diameter nanodiscs revealed a heterogeneous membrane array comprised largely of monomers and dimers, as enumerated by bNAb Fab binding using single-particle electron microscopy analysis, arguing against preferential trimeric association of native MPER and TMD protein segments. Moreover, introduction of isoleucine mutations in the C-terminal heptad repeat to induce an extended MPER α-helical bundle structure yielded an antigenicity profile of cell surface-arrayed Env variants inconsistent with that found in the native prefusion state. In line with these observations, electron paramagnetic resonance analysis suggested that 10E8 inhibits viral membrane fusion by lifting the MPER N-terminal region out of the viralmembrane, mandating the exposure of residues that would be occluded by MPER trimerization. Collectively, our data suggest that the MPER is not a stable trimer, but rather a dynamic segment adapted for structural changes accompanying fusion. [ABSTRACT FROM AUTHOR]

Optimal efficiency of dissolution dynamic nuclear polarization (DNP) is essential to provide the required high sensitivity enhancements for in vitro and in vivo hyperpolarized 13 C nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI). At the nexus of the DNP process are the free electrons, which provide the high spin alignment that is transferred to the nuclear spins. Without changing DNP instrumental conditions, one way to improve 13 C DNP efficiency is by adding trace amounts of paramagnetic additives such as lanthanide (e.g., Gd 3+ , Ho 3+ , Dy 3+ , Tb 3+ ) complexes to the DNP sample, which has been observed to increase solid-state 13 C DNP signals by 100-250%. Herein, we have investigated the effects of paramagnetic transition metal complex R-NOTA (R = Mn 2+ , Cu 2+ , Co 2+ ) doping on the efficiency of 13 C DNP using trityl OX063 as the polarizing agent. Our DNP results at 3.35 T and 1.2 K show that doping the 13 C sample with 3 mM Mn 2+ -NOTA led to a substantial improvement of the solid-state 13 C DNP signal by a factor of nearly 3. However, the other transition metal complexes Cu 2+ -NOTA and Co 2+ -NOTA complexes, despite their paramagnetic nature, had essentially no impact on solid-state 13 C DNP enhancement. W-band electron paramagnetic resonance (EPR) measurements reveal that the trityl OX063 electron T 1 was significantly reduced in Mn 2+ -doped samples but not in Cu 2+ - and Co 2+ -doped DNP samples. This work demonstrates, for the first time, that not all paramagnetic additives are beneficial to DNP. In particular, our work provides a direct evidence that electron T 1 reduction of the polarizing agent by a paramagnetic additive is an essential requirement for the improvement seen in solid-state 13 C DNP signal.

Dissolution dynamic nuclear polarization (DNP) is one of the most successful techniques that resolves the insensitivity problem in liquid-state nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI) by amplifying the signal by several thousand-fold. One way to further improve the DNP signal is the inclusion of trace amounts of lanthanides in DNP samples doped with trityl OX063 free radical as the polarizing agent. In practice, stable monomeric gadolinium complexes such as Gd-DOTA or Gd-HP-DO3A are used as beneficial additives in DNP samples, further boosting the DNP-enhanced solid-state 13 C polarization by a factor of 2 or 3. Herein, we report on the use of a trimeric gadolinium complex as a dopant in 13 C DNP samples to improve the 13 C DNP signals in the solid-state at 3.35 T and 1.2 K and consequently, in the liquid-state at 9.4 T and 298 K after dissolution. Our results have shown that doping the 13 C DNP sample with a complex which holds three Gd 3+ ions led to an improvement of DNP-enhanced 13 C polarization by a factor of 3.4 in the solid-state, on par with those achieved using monomeric Gd 3+ complexes but only requires about one-fifth of the concentration. Upon dissolution, liquid-state 13 C NMR signal enhancements close to 20 000-fold, approximately 3-fold the enhancement of the control samples, were recorded in the nearby 9.4 T high resolution NMR magnet at room temperature. Comparable reduction of 13 C spin-lattice T 1 relaxation time was observed in the liquid-state after dissolution for both the monomeric and trimeric Gd 3+ complexes. Moreover, W-band electron paramagnetic resonance (EPR) data have revealed that 3-Gd doping significantly reduces the electron T 1 of the trityl OX063 free radical, but produces negligible changes in the EPR spectrum, reminiscent of the results with monomeric Gd 3+ -complex doping. Our data suggest that the trimeric Gd 3+ complex is a highly beneficial additive in 13 C DNP samples and that its effect on DNP efficiency can be described in the context of the thermal mixing mechanism.