Alterations of markers related to synaptic function in aging rat brain, in normal conditions or under conditions of long-term dietary manipulation

Neurochemical alterations of markers related to synaptic function are potential candidates for age-related impairment of brain function and cognition. The process of aging, including brain aging, can be counteracted to some degree by maintaning animals in long-term conditions of caloric restriction, or supplementing their diet with antioxidant substances. We report here that the age-related decline of the cholinergic and GABAergic systems, that takes place in some CNS regions of aged rats, is not affected by maintaining them under conditions of dietary restriction and, therefore, of reduced calorie intake, from the 12th to the 30th month of age. We also notice the same lack of effect by adding, during the same period, the aging rat diet with the potential antioxidant substance, N-acetylcysteine (NAC). The same dietary manipulations are also unable to counteract the derangement of the first step of the main biosynthetic pathway for polyamines, putative neuromodulators in the CNS, that occurs in the aged spinal cord. Some age-related alterations in the expression of different subunits of the NMDA-type glutamate receptors in some CNS regions of aged rats were instead, at least in some cases, counteracted by long-term dietary manipulation.     

A semiparametric approach for the two-sample comparison of survival times with long-term survivors

In the two-sample comparison of survival times with long-term survivors, the overall difference between the two distributions reflects differences occurring in early follow-up for susceptible subjects and in long-term follow-up for nonsusceptible subjects. In this setting, we propose statistics for testing (i) no overall, (ii) no short-term, and (iii) no long-term difference between the two distributions to be compared. The statistics are derived as follows. A semiparametric model is defined that characterizes a short-term effect and a long-term effect. By approximating this model about no difference in early survival, a time-dependent proportional hazards model is obtained. The statistics are obtained from this working model. The asymptotic distributions of the statistics for testing no overall or no short-term effects are ascertained, while that of the statistic for testing no long-term effect is valid only when the short-term effect is small. Simulation studies investigate the power properties of the proposed tests for different configurations. The results show the interesting behavior of the proposed tests for situations where a short-term effect is expected. An example investigating the impact of progesterone receptors status on local tumor relapse for patients with early breast cancer illustrates the use of the proposed tests.     

不同类型的棉田生态系统功能特征

通过对 7种不同时空类型的华北棉区棉田生态系统能流、价值流和 N、P、K变化的研究表明 ,华北棉区棉田生态系统的能量生产为 3 0 .41× 1 0 3～ 71 .63× 1 0 3k J/(m2· a) ,纯收入为每 hm2 3 5 65 .80～ 81 46.5 0元 ,主要能量投入为劳动力的投入 ,占总投入能的 75 .80 %～ 81 .1 4%。其在不同时空类型棉田所表现出的变化特征为 :随着播种期的推后 ,棉田内害虫的取食为害作用增加 ,天敌的捕食作用减少 ,光能的利用效率下降 ,棉田经济效益降低 ;实行间套作 ,棉田内害虫的为害作用和天敌的捕食作用均增加 ,光能利用率增加 ,棉田经济效益上升 ;进行免耕种植 ,棉田内害虫的为害取食作用减少 ,天敌的捕食作用增加 ,光能利用率增加 ,棉田经济效益上升。由此进一步探讨了华北棉田生态系统生态调控的途径。     

A novel GLP-1 analog,a dimer of GLP-1 via covalent linkage by a lysine,prolongs the action of GLP-1 in the treatment of type 2 diabetes

GLP-1 is an incretin hormone that can effectively lower blood glucose, however, the short time of biological activity and the side effect limit its therapeutic application. Many methods have been tried to optimize GLP-1 to extend its in vivo half-time, reduce its side effect and enhance its activity. Here we have chosen the idea to dimerize GLP-1 with a C-terminal lysine to form a new GLP-1 analog, DLG3312. We have explored the structure and the biological property of DLG3312, and the results indicated that DLG3312 not only remained the ability to activate the GLP-1R, but also strongly stimulated Min6 cell to secrete insulin. The in vivo bioactivities have been tested on two kinds of animal models, the STZ induced T2DM mice and the db/db mice, respectively. DLG3312 showed potent anti-diabetic ability in glucose tolerance assay and single-dose administration of DLG3312 could lower blood glucose for at least 10 hours. Long-term treatment with DLG3312 can reduce fasted blood glucose, decrease water consumption and food intake and significantly reduce the HbA1c level by 1.80% and 2.37% on STZ induced T2DM mice and the db/db mice, respectively. We also compared DLG3312 with liraglutide to investigate its integrated control of the type 2 diabetes. The results indicated that DLG3312 almost has the same effect as liraglutide but with a much simpler preparation process. In conclusion, we, by using C-terminal lysine as a linker, have synthesized a novel GLP-1 analog, DLG3312. With simplified preparation and improved physiological characterizations, DLG3312 could be considered as a promising candidate for the type 2 diabetes therapy.     

Bat Diversity and Movement in an Agricultural Landscape in Matiguás, Nicaragua

Although agriculture dominates much of Central America, little is known about the bat assemblages that occur within agricultural landscapes and how bats use different types of tree cover within these landscapes. Using mist-nets and a mark-recapture protocol, we compared bat diversity and movement across six types of tree cover within an agricultural landscape in central Nicaragua. The tree cover types surveyed included secondary forests, riparian forests, forest fallows, live fences, pastures with high tree cover and pastures with low tree cover. We captured a total of 3084 bats of 39 species, including two new species records for the country ( Lonchorhina aurita and Molossops greenhalli ). Of these, 2970 bats and 27 species were in the Phyllostomidae family. There were significant differences in mean species density, abundance and evenness of phyllostomid bats across the different types of tree cover, but not in bat diversity. Riparian forests had the highest mean species density and bat abundance per plot. In contrast, mean bat abundance and species density were lowest in pastures with low tree cover. Of the 1947 phyllostomid bats marked, a total of 64 bats of eight species were recaptured. The average linear distance between extra-site recaptures was 2227 m (± 228 SE) and the maximum distance was 10.6 km. Bats were recorded moving between almost all types of tree cover, and especially to and from riparian forests. Our study suggests that agricultural landscapes retaining a heterogeneous tree cover may maintain a diverse bat assemblage, and that bats visit and use a variety of tree cover types within the agricultural matrix.     

1-Hydroxypyrazole as a bioisostere of the acetic acid moiety in a series of aldose reductase inhibitors

Therapeutic intervention with aldose reductase inhibitors appears to be promising for major pathological conditions (i.e., long-term diabetic complications and inflammatory pathologies). So far, however, clinical candidates have failed due to adverse side-effects (spiroimides) or poor bioavailability (carboxylic acids). In this work, we succeeded in the bioisosteric replacement of an acetic acid moiety with that of 1-hydroxypyrazole. This new scaffold appears to have a superior physicochemical profile, while attaining inhibitory activity in the submicromolar range.     

A brain-inspired compact cognitive mapping system

In many simultaneous localization and mapping (SLAM) systems, the map of the environment grows over time as the robot explores the environment. The ever-growing map prevents long-term mapping, especially in large-scale environments. In this paper, we develop a compact cognitive mapping approach inspired by neurobiological experiments. Mimicking the firing activities of neighborhood cells, neighborhood fields determined by movement information, i.e. translation and rotation, are modeled to describe one of the distinct segments of the explored environment. The vertices with low neighborhood field activities are avoided to be added into the cognitive map. The optimization of the cognitive map is formulated as a robust non-linear least squares problem constrained by the transitions between vertices, and is numerically solved efficiently. According to the cognitive decision-making of place familiarity, loop closure edges are clustered depending on time intervals, and then batch global optimization of the cognitive map is performed to satisfy the combined constraint of the whole cluster. After the loop closure process, scene integration is performed, in which revisited vertices are removed subsequently to further reduce the size of the cognitive map. The compact cognitive mapping approach is tested on a monocular visual SLAM system in a naturalistic maze for a biomimetic animated robot. Our results demonstrate that the proposed method largely restricts the growth of the size of the cognitive map over time, and meanwhile, the compact cognitive map correctly represents the overall layout of the environment. The compact cognitive mapping method is well suitable for the representation of large-scale environments to achieve long-term robot navigation. Electronic supplementary materialThe online version of this article (10.1007/s11571-020-09621-6) contains supplementary material, which is available to authorized users.     

Long-term low-dose α-particle enhanced the potential of malignant transformation in human bronchial epithelial cells through MAPK/Akt pathway

Since the wide usage of ionizing radiation, the cancer risk of low dose radiation (LDR) (<0.1 Gy) has become attractive for a long time. However, most results are derived from epidemiologic studies on atomic-bomb survivors and nuclear accidents surrounding population, and the molecular mechanism of this risk is elusive. To explore the potential of a long-term LDR-induced malignant transformation, human bronchial epithelial cells Beas-2B were fractionally irradiated with 0.025 Gy α-particles for 8 times in total and then further cultured for 1–2 months. It was found that the cell proliferation, the abilities of adhesion and invasion, and the protein expressions of p-ERK, p-Akt, especially p-P38 were not only increased in the multiply-irradiated cells but also in their offspring 1–2 months after the final exposure, indicating high potentiality of cell malignant transformation. On opposite, the expressions of p-JNK and p-P66 were diminished in the subcultures of irradiated cells and thus may play a role of negative regulation in canceration. When the cells were transferred with p38 siRNA, the LDR-induced enhancements of cell adhesion and invasion were significantly reduced. These findings suggest that long-term LDR of α-particles could enhance the potential of malignant transformation incidence in human bronchial epithelial cells through MAPK/Akt pathway.     

Revision and quality analyses of the Helgoland Reede long-term phytoplankton data archive

The Biological Station on Helgoland has one of the longest data series for phytoplankton species composition in the world. Since 1962, phytoplankton has been counted to a species level on a daily basis (weekdays). One of the main reasons why this data set has rarely been used is that it has never been subjected to proper quality control or inventoried properly. This paper describes the quality control which we have now carried out on this data set and also represents the first inventory of the data and its meta-information. A comparison of the electronic database where the data is archived and the original recorded lists from the different persons dealing with the samples was an integral part of the evaluation. Apart from recording inconsistencies in species identification, we also recorded and corrected the many differences found between the electronic and paper data. The evaluation was carried out in a direct comparative manner to discern taxonomic discrepancies, and in order to find random errors in the transfer of data from paper to computer random checks of the data were carried out. This paper serves to illustrate the level of quality control required when dealing with archived phytoplankton data and illustrates the typical problems encountered.Communicated by H.-D. Franke