Muramyl dipeptide induced augmentation of the proliferative response of thymocytes to phytohemagglutinin

N-Acetylmuramyl-L-alanyl-D-isoglutamine (MDP) augmented the proliferative response of thymocytes to phytohemagglutinin (PHA). The augmenting effect of MDP disappeared by passage of glass-nonadherent thymocytes through Sephadex G-10 (G-10) column or by removal of low density cells by the Ficoll-Conray gradient centrifugation. The diminished augmenting effects of MDP on the proliferative response of glass-nonadherent-G-10 nonadherent thymocytes was restored by the addition of the G-10 adherent cells. When G-10 adherent cell fraction was extensively depleted of macrophages by glass adherence and EA-rosetting, it was found that neither the macrophage-depleted G-10 adherent cell fraction nor the macrophage fraction supported by itself the proliferative response of G-10 nonadherent thymocytes. However, addition of macrophage fraction together with the macrophage-depleted G-10 adherent cells did support the proliferation of G-10 nonadherent thymocytes. It was further shown that peritoneal exudate macrophages could be substituted for thymic macrophage fraction. These results suggested that both the G-10 adherent-glass nonadherent cells and macrophages were essential for the MDP-induced augmentation of the proliferative response of thymocytes to PHA and these cells exerted different accessory roles in this response.     

Calcium Ions Modulate the Mechanics of Tomato Bushy Stunt Virus

Viral particles are endowed with physicochemical properties whose modulation confers certain metastability to their structures to fulfill each task of the viral cycle. Here, we investigate the effects of swelling and ion depletion on the mechanical stability of individual tomato bushy stunt virus nanoparticles (TBSV-NPs). Our experiments show that calcium ions modulate the mechanics of the capsid: the sequestration of calcium ions from the intracapsid binding sites reduces rigidity and resilience in ∼24% and 40%, respectively. Interestingly, mechanical deformations performed on native TBSV-NPs induce an analogous result. In addition, TBSV-NPs do not show capsomeric vacancies after surpassing the elastic limit. We hypothesize that even though there are breakages among neighboring capsomers, RNA-capsid protein interaction prevents the release of capsid subunits. This work shows the mechanical role of calcium ions in viral shell stability and identifies TBSV-NPs as malleable platforms based on protein cages for cargo transportation at the nanoscale.     

The Role of Surgeon-Performed Office and Preincision Ultrasounds in Localization of Parathyroid Adenomas in Primary Hyperparathyroidism

ObjectiveWe studied the use of surgeon-performed office ultrasound (OU) and preincision ultrasound (PIU) in preoperatively localizing parathyroid adenomas in primary hyperparathyroidism (PHPT).MethodsA retrospective chart review was performed for patients with PHPT who underwent parathyroidectomy between 2013 and 2015. The results of OU and PIU were recorded and compared with the final surgical pathology.ResultsOf 348 patients with PHPT, 285 (81.9%) had single-lesion disease, 49 (14.1%) had double-lesion disease, and 14 (4.0%) had multigland disease with 3 or more lesions. For single-lesion disease, the overall sensitivity and specificity of OU to correctly lateralize the lesion were 64.2% and 91.2%, while those of PIU were 89.4% and 93.6%, respectively. The sensitivity and specificity of PIU were comparable to those of 4-dimensional computed tomography (87.1% and 90.7%, respectively) and ^99mTc-sestamibi scintigraphy (70.4% and 95.9%, respectively). While the majority of PIU cases were preceded by other imaging studies, the accuracy in localizing lesions was not largely affected by the presence of prior computed tomography and/or ^99mTc-sestamibi scintigraphy, as opposed to ultrasounds only. For detecting the presence of multigland disease, the sensitivity and specificity of OU were 26% and 92.2%, while those of PIU were 64.3% and 94.7%, respectively.ConclusionSurgeon-performed OU and PIU are valuable tools in preoperatively localizing the parathyroid adenoma in single-lesion disease, while their utility may be limited for double-lesion or multigland disease. PIU in particular yields high accuracy in detecting parathyroid lesions in combination with other imaging modalities.     

Microgeographic variation in early fitness traits of Pinus sylvestris from contrasting soils

Premise

The possibility of fine-scale intraspecific adaptive divergence under gene flow is established by theoretical models and has been confirmed empirically in tree populations distributed along steep altitudinal clines or across extreme edaphic discontinuities. However, the possibility of microgeographic adaptive divergence due to less severe but more frequent kinds of soil variation is unclear.

Methods

In this study, we looked for evidence of local adaptation to calcareous versus siliceous soil types in two nearby Mediterranean Pinus sylvestris populations connected via pollen flow. Using a greenhouse experiment, we tested for variation in early (up to three years of age) seedling performance among open-pollinated maternal families originating from each edaphic provenance when experimentally grown on both types of natural local substrate.

Results

Although seedlings were clearly affected by the edaphic environment, exhibiting lower and slower emergence as well as higher mortality on the calcareous than in the siliceous substrate, neither the performance on each substrate nor the plasticity among substrates varied significantly with seedling edaphic provenance.

Conclusions

We found no evidence of local adaptation to a non-extreme edaphic discontinuity over a small spatial scale, at least during early stages of seedling establishment. Future studies on microgeographic soil-driven adaptation should consider long-term experiments to minimize maternal effects and allow a potentially delayed expression of edaphic adaptive divergence.     

Ugi Bis-Amide Derivatives as Tyrosinase Inhibitor; Synthesis,Biology Assessment,and in Silico Analysis

Herein, a straightforward synthetic strategy mediated by Ugi reaction was developed to synthesize novel series of compounds as tyrosinase inhibitors. The structures of all compounds were confirmed by FT-IR, ¹H-NMR, ¹³C-NMR, and CHNOS techniques. The tyrosinase inhibitory activities of all synthesized derivatives 5a – m were determined against mushroom tyrosinase and it was found that derivative 5c possesses the best inhibition with an IC₅₀ value of 69.53±0.042 μM compared to the rest of the synthesized derivatives. Structure–activity relationships (SARs) showed that the presence of 4-MeO or 4-NO₂ at the R² position plays a key role in tyrosinase inhibitory activities. The enzyme kinetics studies showed that compound 5c is an noncompetitive inhibitor. For in silico study, the allosteric site detection was first applied to find the appropriate binding site and then molecular docking and molecular dynamic studies were performed to reveal the position and interactions of 5c as the most potent inhibitor within the tyrosinase active site. The results showed that 5c bind well with the proposed binding site and formed a stable complex with the target protein.     

Molecular orbital studies of the action of thyroid hormone analogs: Effects on oxygen consumption of mitochondria and horseradish peroxidase-catalyzed NADH oxidation

The electronic structure of thyroxine and related compounds were calculated by semiempirical molecular orbital methods. When the quantum chemical indices obtained were compared with the structure-activity relationship obtained so far byin vivo andin vitro assays, it was found that HOMO (highest occupied molecular orbital) energy levels of thyroxine and its analogs are well correlated with the increase in oxygen consumption of rat kidney mitochondria determined byin vitro assay. This finding permits the hypothesis that these compounds may play a role in activating the electron transport system of mitochondria by mediating the oxidation-reduction of cytochromes. Furthermore, HOMO energy levels of thyroxine and phenol derivatives were found to correlate well with the stimulation of horseradish peroxidase-catalyzed oxidation of NADH. This suggests that the step of electron removal from these compounds by the enzyme system may be a rate-limiting step, confirming the view that phenoxy-radicals meditate the whole reaction.     

Investigating above-ground biomass in old-growth and secondary montane forests of the Cameroon Highlands

Tropical montane forests can store and sequester substantial amounts of carbon in above-ground biomass (AGB), but variations in this storage related to location or degradation have not been quantified in the Cameroon Highlands. We established 25 permanent plots (20 m × 40 m) and sampled all trees ≥10 cm diameter following standard RAINFOR protocols. We estimated AGB and investigated variations related to taxonomic and structural forest attributes, including the height–diameter allometry in five forest types (four old-growth dominated by different species and one secondary forest). Secondary forests had significantly lower AGB than old-growth forests (49.4 ± 2.5 vs. >476.3 ± 168.7 Mg/ha, respectively), mostly related to lower basal area and tree height. Significant differences in species composition but not in forest structure or AGB were found between the four types of old-growth forests studied, located at different altitudes and mountains. We discuss the importance of these montane forests for carbon storage and, considering their high diversity and current threats, their potential for carbon finance mechanisms related to both avoided deforestation and forest restoration.