The Wobbler Mouse Model of Amyotrophic Lateral Sclerosis (ALS) Displays Hippocampal Hyperexcitability,and Reduced Number of Interneurons,but No Presynaptic Vesicle Release Impairments

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease. It is a fatal degenerative disease, best recognized for its debilitating neuromuscular effects. ALS however also induces cognitive impairments in as many as 50% of affected individuals. Moreover, many ALS patients demonstrate cortical hyperexcitability, which has been shown to precede the onset of clinical symptoms. The wobbler mouse is a model of ALS, and like ALS patients the wobbler mouse displays cortical hyperexcitability. Here we investigated if the neocortical aberrations of the wobbler mouse also occur in the hippocampus. Consequently, we performed extracellular field excitatory postsynaptic potential recordings in the CA1 region of the hippocampus on acute brain slices from symptomatic (P45-P60) and presymptomatic (P17-P21) wobbler mice. Significant increased excitation of hippocampal synapses was revealed by leftward shifted input/output-curves in both symptomatic and presymptomatic wobbler mice, and substantiated by population spike occurrence analyses, demonstrating that the increased synaptic excitation precedes the onset of visible phenotypic symptoms in the mouse. Synaptic facilitation tested by paired-pulse facilitation and trains in wobbler and control mice showed no differences, suggesting the absence of presynaptic defects. Immunohistochemical staining revealed that symptomatic wobbler mice have a lower number of parvalbumin positive interneurons when compared to controls and presymptomatic mice. This study reveals that the wobbler mouse model of ALS exhibits hippocampal hyperexcitability. We suggest that the hyperexcitability could be caused by increased excitatory synaptic transmission and a concomitant reduced inhibition due to a decreased number of parvalbumin positive interneurons. Thus we substantiate that wobbler brain impairments are not confined to the motor cortex, but extend to the hippocampus. Importantly, we have revealed more details of the early pathophysiology in asymptomatic animals, and studies like the present may facilitate the development of novel treatment strategies for earlier intervention in ALS patients in the future.     

Integrated Intercalation‐Based and Interfacial Sodium Storage in Graphene‐Wrapped Porous Li4Ti5O12 Nanofibers Composite Aerogel

Sodium storage in both solid–liquid and solid–solid interfaces is expected to extend the horizon of sodium‐ion batteries, leading to a new strategy for developing high‐performance energy‐storage materials. Here, a novel composite aerogel with porous Li₄Ti₅O₁₂ (PLTO) nanofibers confined in a highly conductive 3D‐interconnected graphene framework (G‐PLTO) is designed and fabricated for Na storage. A high capacity of 195 mA h g^?1 at 0.2 C and super‐long cycle life up to 12 000 cycles are attained. Electrochemical analysis shows that the intercalation‐based and interfacial Na storage behaviors take effect simultaneously in the G‐PLTO composite aerogel. An integrated Na storage mechanism is proposed. This study ascribes the excellent performance to the unique structure, which not only offers short pathways for Na⁺ diffusion and conductive networks for electron transport, but also guarantees plenty of PLTO–electrolyte and PLTO–graphene interfacial sites for Na⁺ adsorption.     

Difference in 24-Hour Urine Composition between Diabetic and Non-Diabetic Adults without Nephrolithiasis

Background

Diabetic patients are more likely to develop kidney stones than the general population. The underlying mechanisms for this disparity remain to be elucidated. Little is known about the relationship between urine composition and diabetes mellitus in non-stone-forming individuals. We sought to examine the differences in the 24-hour (24-h) urine composition between diabetic and non-diabetic adults who were not stone formers.

Methods

A convenience sample of 538 individuals without a history of nephrolithiasis, gout, hyperparathyroidism, or gastroenteric diseases participated in this study. The 24-h urine profiles of 115 diabetic adults were compared with those of 423 non-diabetic adults. Diabetes was defined by self-reported physician diagnosis or medication use. All participants were non-stone formers confirmed by urinary tract ultrasonography. Participants provided a fasting blood sample and a single 24-h urine collection for stone risk analysis. Student’s t-test was used to compare mean urinary values. Linear regression models were adjusted for age, gender, body mass index, hypertension, fasting serum glucose, serum total cholesterol, estimated creatinine clearance rate and urinary factors.

Results

Univariable analysis showed that the diabetic participants had significantly higher 24-h urine volumes and lower urine calcium and magnesium excretions than non-diabetic participants (all P < 0.05). After multivariate adjustment, no significant differences in 24-h urine composition were observed between diabetic and non-diabetic participants except for a slightly increased 24-h urine volume in diabetic participants (all P > 0.05). The main limitation of this study is that the convenience samples and self-reported data may have been sources of bias.

Conclusion

Our data showed that there were no differences in 24-h urine composition between diabetic and non-diabetic adults who are not stone formers. The reason for it might be the improved glycemic control in diabetic individuals in our study. Therefore, a tighter glycemic control might reduce stone formation in diabetic adults.     

A Map-Based Service Supporting Different Types of Geographic Knowledge for the Public

The internet enables the rapid and easy creation, storage, and transfer of knowledge; however, services that transfer geographic knowledge and facilitate the public understanding of geographic knowledge are still underdeveloped to date. Existing online maps (or atlases) can support limited types of geographic knowledge. In this study, we propose a framework for map-based services to represent and transfer different types of geographic knowledge to the public. A map-based service provides tools to ensure the effective transfer of geographic knowledge. We discuss the types of geographic knowledge that should be represented and transferred to the public, and we propose guidelines and a method to represent various types of knowledge through a map-based service. To facilitate the effective transfer of geographic knowledge, tools such as auxiliary background knowledge and auxiliary map-reading tools are provided through interactions with maps. An experiment conducted to illustrate our idea and to evaluate the usefulness of the map-based service is described; the results demonstrate that the map-based service is useful for transferring different types of geographic knowledge.     

华癸根瘤菌7653R中一个RND型药物外排泵的功能表型及调控鉴定

【目的】研究华癸根瘤菌7653R中MCHK_0866和MCHK_0867编码的RND家族外排泵的功能表型。【方法】对外排泵编码基因及候选调控基因在基因组上的结构进行分析。采用测定OD_(600)观察菌株生长曲线的变化。通过测定最低抑菌浓度检测菌株的药物敏感性,RT-PCR检测目的基因经特定物质处理后表达量的变化。通过细菌单杂交系统初步检测外排泵的转录调控。【结果】MCHK_0866和MCHK_0867所编码蛋白共同组成一个RND家族射流泵。缺失该外排泵后,细菌生长曲线在稳定期OD_(600)数值降低,对萘啶酸、四环素和SDS的敏感性发生变化,萘啶酸处理细菌后2个基因的表达量增加。同时,下游属于Tet R转录因子家族的基因MCHK_0869表达产物作用于MCHK_0867的启动子区域。【结论】该外排泵与萘啶酸的运输有关,缺失后自身生长受到影响,表达受到下游转录因子的调控。     

A novel procedure for the assessment of the antioxidant capacity of food components

Carbonylation, an oxidative modification of the amino group of arginine and lysine residues caused by reactive oxygen species, has emerged as a new type of oxidative damage. Protein carbonylation has been shown to exert adverse effects on various protein functions. Recently, the role of food components in the attenuation of oxidative stress has been the focus of many studies. Most of these studies focused on the chemical properties of food components. However, it is also important to determine their effects on protein functions via post-translational modifications. In this study, we developed a novel procedure for evaluating the antioxidant capacity of food components. Hydrogen peroxide (H₂O₂)-induced protein carbonylation in HL-60 cells was quantitatively analyzed by using fluorescent dyes (Cy5–hydrazide dye and IC3–OSu dye), followed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE) and fluorescence determination. Among a panel of food components tested, quinic acid, kaempferol, saponin, squalene, trigonelline, and mangiferin were shown to be capable of suppressing protein carbonylation in HL-60 cells. Our results demonstrated that this fluorescence labeling/SDS–PAGE procedure allows for the detection of oxidative stress-induced protein carbonylation with high sensitivity and quantitative accuracy. This method should be useful for the screening of new antioxidant food components as well as the analysis of their suppression mechanism.     

Multiple mechanisms contributed to the reduced stability of Inner Mongolia grassland ecosystem following nitrogen enrichment

Plant and Soil - Global nitrogen enrichment has been identified as a major environmental problem that poses a threat to ecosystem functioning. However, there is no consensus on the impact of...     

Cohesin acetylation and Wapl‐Pds5 oppositely regulate translocation of cohesin along DNA

Cohesin is a ring‐shaped protein complex that plays a crucial role in sister chromatid cohesion and gene expression. The dynamic association of cohesin with chromatin is essential for these functions. However, the exact nature of cohesin dynamics, particularly cohesin translocation, remains unclear. We evaluated the dynamics of individual cohesin molecules on DNA and found that the cohesin core complex possesses an intrinsic ability to traverse DNA in an adenosine triphosphatase (ATPase)‐dependent manner. Translocation ability is suppressed in the presence of Wapl‐Pds5 and Sororin; this suppression is alleviated by the acetylation of cohesin and the action of mitotic kinases. In Xenopus laevis egg extracts, cohesin is translocated on unreplicated DNA in an ATPase‐ and Smc3 acetylation‐dependent manner. Cohesin movement changes from bidirectional to unidirectional when cohesin faces DNA replication; otherwise, it is incorporated into replicating DNA without being translocated or is dissociated from replicating DNA. This study provides insight into the nature of individual cohesin dynamics and the mechanisms by which cohesin achieves cohesion in different chromatin contexts.