Corticotroph,somatotroph and mammotroph cell kinetics in the postnatal infant female rat

The aim of this work was to detect if hypothalamic-pituitary maturation was accompanied by significant proliferation changes in differentiated pituitary cell pools. For this purpose, pituitary corticotroph (Ct), mammotroph (Mt) and somatotroph (St) proliferation activities were scanned in intact female rats during the postnatal (P) period (1–35 postnatal days). The techniques of tritiated thymidine labelling, immunostaining and autoradiography were combined to visualize DNA synthesis of hormone containing cells. Immunoreactive cell densities were measured using image analysis, and double labelled cells were counted. Corticotroph proliferation activity increased significantly on day P12, followed by an increase in the Ct proportion on days P13–14. This is the first observation of a spontaneous change of corticotroph proliferation at the end of the stress nonresponsive period. The mammotroph density and proliferation rate increased gradually during postnatal maturation, until the Mt pool overran other cell types of the female hypophysis on day 35. The somatotroph pool was the most numerous until day P20; the proliferation rate remained constant while St proportions increased reaching a plateau between days P13 and 20, then decreased to the adult level. Each cell type examined showed a characteristic, individual density and proliferation pattern.     

Effects of reconstruction methods on dose distribution for lung stereotactic body radiotherapy treatment plans

Radiation and Environmental Biophysics - The aim of the present study was to investigate the effect of tumour motion on various imaging strategies as well as on treatment plan accuracy for lung...     

眼小叶蝉属和东半球眼小叶蝉族评述：（头喙亚目,叶蝉科,小叶蝉亚科）

本文首先根据眼小叶蝉族Alebrini讨论翅的命名,接着是眼小叶蝉属Alebra Fieb.和东半球眼小叶蝉族各属的评论。Homa elongata Kato移入属AsialebraDwor.,Shaddai distanti Dwor.是S.typicus Dist.的异名。描述了6个新种,即Sobralacapreola,S.clara,Orientalebra drawidana,Afralebra melichari,A.youngi,A.paolii. 本文引言部分讨论小叶蝉亚科Typhlocybinae翅的形态学,正文为分类部分。 在描述内部构造以及端节、头、和胸部背面时,使用习惯术语。 新种模式标本系列保存于下列博物馆中;正模的保管者在有关描述中最先提到: SMTD——德国得累斯顿,国家动物学博物馆。 BMNH——英国伦敦,英国自然历史博物馆。 USNM——美国华盛顿,美国国家博物馆。 MM——捷克斯洛伐克Brno,Moravian博物馆。     

In Silico Design of an Oseltamivir Derivative with Increased Affinity against Wild-Type and Mutant Variants of Neuraminidase and Hemagglutinin of Influenza A H1N1 Virus

Antiviral resistance has turned into a world concern nowadays. Influenza A H1N1 emerged as a problem at the world level due to the neuraminidase (NA) mutations. The NA mutants conferred resistance to oseltamivir and zanamivir. Several efforts were conducted to develop better anti-influenza A H1N1 drugs. Our research group combined in silico methods to create a compound derived from oseltamivir to be tested in vitro against influenza A H1N1. Here we show the results of a new compound derived from oseltamivir but with specific chemical modifications, with significant affinity either on NA (in silico and in vitro assays) or HA (in silico) from influenza A H1N1 strain. We include docking and molecular dynamics (MD) simulations of the oseltamivir derivative at the binding site onto NA and HA of influenza A H1N1. Additionally, the biological experimental results show that oseltamivir derivative decreases the lytic-plaque formation on viral susceptibility assays, and it does not show cytotoxicity. Finally, oseltamivir derivative assayed on viral NA showed a concentration-dependent inhibition behavior at nM, depicting a high affinity of the compound for the enzyme, corroborated with the MD simulations results, placing our designed oseltamivir derivative as a potential antiviral against influenza A H1N1.     

Synthesis,Biological Evaluation,and Molecular Modeling Studies of New 1,3,4-Thiadiazole Derivatives as Potent Antimicrobial Agents

In this work, the synthesis, characterization, and biological activities of a new series of 1,3,4-thiadiazole derivatives were investigated. The structures of final compounds were identified using ¹H-NMR, ¹³C-NMR, elemental analysis, and HRMS. All the new synthesized compounds were then screened for their antimicrobial activity against four types of pathogenic bacteria and one fungal strain, by application of the MIC assays, using Ampicilin, Gentamycin, Vancomycin, and Fluconazole as standards. Among the compounds, the MIC values of 4 and 8 μg/mL of the compounds 3f and 3g , respectively, are remarkable and indicate that these compounds are good candidates for antifungal activity. The docking experiments were used to identify the binding forms of produced ligands with sterol 14-demethylase to acquire insight into relevant proteins. The MD performed about 100 ns simulations to validate selected compounds’ theoretical studies. Finally, using density functional theory (DFT) to predict reactivity, the chemical characteristics and quantum factors of synthesized compounds were computed. These results were then correlated with the experimental data. Furthermore, computational estimation was performed to predict the ADME properties of the most active compound 3f .     

Modelling motor units in 3D: influence on muscle contraction and joint force via a proof of concept simulation

Functional heterogeneity is a skeletal muscle’s ability to generate diverse force vectors through localised motor unit (MU) recruitment. Existing 3D macroscopic continuum-mechanical finite element (FE) muscle models neglect MU anatomy and recruit muscle volume simultaneously, making them unsuitable for studying functional heterogeneity. Here, we develop a method to incorporate MU anatomy and information in 3D models. Virtual fibres in the muscle are grouped into MUs via a novel “virtual innervation” technique, which can control the units’ size, shape, position, and overlap. The discrete MU anatomy is then mapped to the FE mesh via statistical averaging, resulting in a volumetric MU distribution. Mesh dependency is investigated using a 2D idealised model and revealed that the amount of MU overlap is inversely proportional to mesh dependency. Simultaneous recruitment of a MU’s volume implies that action potentials (AP) propagate instantaneously. A 3D idealised model is used to verify this assumption, revealing that neglecting AP propagation results in a slightly less-steady force, advanced in time by approximately 20 ms, at the tendons. Lastly, the method is applied to a 3D, anatomically realistic model of the masticatory system to demonstrate the functional heterogeneity of masseter muscles in producing bite force. We found that the MU anatomy significantly affected bite force direction compared to bite force magnitude. MU position was much more efficacious in bringing about bite force changes than MU overlap. These results highlight the relevance of MU anatomy to muscle function and joint force, particularly for muscles with complex neuromuscular architecture.

     

Comparative LCA studies of simulated HMF biorefineries from maize and miscanthus as an example of first- and second-generation biomass as a tool for process development

5-Hydroxymethylfurfural (HMF) is a versatile platform chemical for a fossil free, bio-based chemical industry. HMF can be produced by using fructose as a feedstock. Using edible, first-generation biomass to produce chemicals has been questioned in terms of potential competition with food supply. Second-generation biomass like miscanthus could be an alternative. However, there is a lack of information if second-generation lignocellulosic biomass is a more sustainable feedstock to produce HMF. Therefore, a life cycle assessment was performed in this study to determine the environmental impacts of HMF production from miscanthus and to compare it with HMF from high-fructose corn syrup (HFCS). HFCS from either Hungary or Baden-Württemberg (Germany) was considered. Compared to the HFCS biorefineries the miscanthus concept is producing less emissions in all impact categories studied, except land occupation. Overall, the production and usage of second-generation biomass could be especially beneficial in areas where the use of N fertilizers is restricted. Besides, conclusions for the further development of the on-farm biorefinery concept were elaborated. For this purpose, process simulations from a previous study were used. Results of the previous study in terms of TEA and the current LCA study in terms of environmental sustainability indicate that the lignin depolymerization unit in the miscanthus biorefinery has to be improved. The scenario without lignin depolymerization performs better in all impact categories. The authors recommend to not further convert the lignin to products like phenol and other aromatic compounds. The results of the contribution analyses show that the major impact in the HMF production is caused by the auxiliary materials in the separation units and the required heat. Further technical development should focus on efficient heat as well as solvent use and solvent recovery. At this point further optimizations will lead to reduced emissions and costs at the same time.     

Comparison of mechanistic and hybrid modeling approaches for characterization of a CHO cultivation process: Requirements,pitfalls and solution paths

Despite the advantages of mathematical bioprocess modeling, successful model implementation already starts with experimental planning and accordingly can fail at this early stage. For this study, two different modeling approaches (mechanistic and hybrid) based on a four-dimensional antibody-producing CHO fed-batch process are compared. Overall, 33 experiments are performed in the fractional factorial four-dimensional design space and separated into four different complex data partitions subsequently used for model comparison and evaluation. The mechanistic model demonstrates the advantage of prior knowledge (i.e., known equations) to get informative value relatively independently of the utilized data partition. The hybrid approach displayes a higher data dependency but simultaneously yielded a higher accuracy on all data partitions. Furthermore, our results demonstrate that independent of the chosen modeling framework, a smart selection of only four initial experiments can already yield a very good representation of a full design space independent of the chosen modeling structure. Academic and industry researchers are recommended to pay more attention to experimental planning to maximize the process understanding obtained from mathematical modeling.