Interactions of Amyloid-β with Membrane Proteins

In developing and developed countries, an increasing elderly population is observed. This affects the growing percentage of people struggling with neurodegenerative diseases, including Alzheimer’s disease. Nevertheless, the pathomechanism of this disease is still unknown. This contributes to problems with early diagnosis of the disease as well as with treatment. One of the most popular hypotheses of Alzheimer’s disease is related to the pathological deposition of amyloid-β (Aβ) in the brain of ill people. In this paper, we discuss issues related to Aβ and its relationship in the development of Alzheimer’s disease. The structure of Aβ and its interaction with the cell membrane are discussed. Not only do the extracellular plaques affect nerve cells, but other forms of this peptide as well.     

Interaction between Lipopolysaccharide and Gut Microbiota in Inflammatory Bowel Diseases

Lipopolysaccharides (LPSs) are bacterial surface glycolipids, produced by Gram-negative bacteria. LPS is known to determine acute inflammatory reactions, particularly in the context of sepsis. However, LPS can also trigger chronic inflammation. In this case, the source of LPS is not an external infection, but rather an increase in endogenous production, which is usually sustained by gut microbiota (GM), and LPS contained in food. The first site in which LPS can exert its inflammatory action is the gut: both GM and gut-associated lymphoid tissue (GALT) are influenced by LPS and shift towards an inflammatory pattern. The changes in GM and GALT induced by LPS are quite similar to the ones seen in IBD: GM loses diversity, while GALT T regulatory (Tregs) lymphocytes are reduced in number, with an increase in Th17 and Th1 lymphocytes. Additionally, the innate immune system is triggered, through the activation of toll-like receptor (TLR)-4, while the epithelium is directly damaged, further triggering inflammation. In this review, we will discuss the importance of the crosstalk between LPS, GM, and GALT, and discuss the possible implications.     

Amyloid Beta-Mediated Changes in Synaptic Function and Spine Number of Neocortical Neurons Depend on NMDA Receptors

Onset and progression of Alzheimer’s disease (AD) pathophysiology differs between brain regions. The neocortex, for example, is a brain region that is affected very early during AD. NMDA receptors (NMDARs) are involved in mediating amyloid beta (Aβ) toxicity. NMDAR expression, on the other hand, can be affected by Aβ. We tested whether the high vulnerability of neocortical neurons for Aβ-toxicity may result from specific NMDAR expression profiles or from a particular regulation of NMDAR expression by Aβ. Electrophysiological analyses suggested that pyramidal cells of 6-months-old wildtype mice express mostly GluN1/GluN2A NMDARs. While synaptic NMDAR-mediated currents are unaltered in 5xFAD mice, extrasynaptic NMDARs seem to contain GluN1/GluN2A and GluN1/GluN2A/GluN2B. We used conditional GluN1 and GluN2B knockout mice to investigate whether NMDARs contribute to Aβ-toxicity. Spine number was decreased in pyramidal cells of 5xFAD mice and increased in neurons with 3-week virus-mediated Aβ-overexpression. NMDARs were required for both Aβ-mediated changes in spine number and functional synapses. Thus, our study gives novel insights into the Aβ-mediated regulation of NMDAR expression and the role of NMDARs in Aβ pathophysiology in the somatosensory cortex.     

Adipose-Derived Stem Cells in the Treatment of Perianal Fistulas in Crohn’s Disease: Rationale,Clinical Results and Perspectives

Between 20 to 25% of Crohn’s disease (CD) patients suffer from perianal fistulas, a marker of disease severity. Seton drainage combined with anti-TNFα can result in closure of the fistula in 70 to 75% of patients. For the remaining 25% of patients there is room for in situ injection of autologous or allogenic mesenchymal stem cells such as adipose-derived stem/stromal cells (ADSCs). ADSCs exert their effects on tissues and effector cells through paracrine phenomena, including the secretome and extracellular vesicles. They display anti-inflammatory, anti-apoptotic, pro-angiogenic, proliferative, and immunomodulatory properties, and a homing within the damaged tissue. They also have immuno-evasive properties allowing a clinical allogeneic approach. Numerous clinical trials have been conducted that demonstrate a complete cure rate of anoperineal fistulas in CD ranging from 46 to 90% of cases after in situ injection of autologous or allogenic ADSCs. A pivotal phase III-controlled trial using allogenic ADSCs (Alofisel^®) demonstrated that prolonged clinical and radiological remission can be obtained in nearly 60% of cases with a good safety profile. Future studies should be conducted for a better knowledge of the local effect of ADSCs as well as for a standardization in terms of the number of injections and associated procedures.     

40CrNiMo钢轴开裂原因分析

通过对40CrNiMo钢轴取样进行化学成分分析、硬度检测和金相高低倍观察,结合钢轴断口形貌检验,分析讨论了钢轴产生开裂的原因,并针对原因提出了改进措施。结果表明:芯部存在较严重的带状组织偏析是导致钢轴开裂的主要原因,调质热处理过程中形成的上贝氏体进一步降低了材料性能,促进了裂纹形成和扩展。     

Self-sufficient Cytochrome P450s and their potential applications in biotechnology

Cytochrome P450s(CYPs) are ubiquitously found in all kingdoms of life, playing important role in various biosynthetic pathways as well as degradative pathways; accordingly find applications in a vast variety of areas from organic synthesis and drug metabolite production to modification of biomaterials and bioremediation.Significantly, CYPs catalyze chemically challenging C—H and C—C activation reactions using a reactive high-valent iron-oxo intermediate generated upon dioxygen activation at their heme center,while the other oxygen atom is reduced to the level of water by electrons provided through a reductase partner protein.Self-sufficient CYPs, encoding their heme domain and reductase protein in a single polypeptide, facilitate increased catalytic efficiency and render a less complicated system to work with.The self-sufficient CYP enzyme from CYP102A family(CYP102A1, BM3) is among the earliest and most-investigated model enzymes for mechanistic and structural studies as well as for biotechnological applications.An increasing number of self-sufficient CYPs from the same CYP102 family and from other families have also been reported in last decade.In this review, we introduce chemistry and biology of CYPs, followed by an overview of the characteristics of self-sufficient CYPs and representative reactions.Enzyme engineering efforts leading to novel self-sufficient CYP variants that can catalyze synthetically useful natural and non-natural(nature-mimicking) reactions are highlighted.Lastly, the strategy and efforts that aim to circumvent the challenges for improved thermostability, regio-and enantioselectivity,and total turnover number; associated with practical use of self-sufficient CYPs are reviewed.     

Effect of heat treatment on the synthesis of hydroxyapatite from Indian clam seashell by hydrothermal method

Hydroxyapatite (HA) powder has been successfully synthesized from low-cost Indian clam seashells by using hydrothermal method. The mixture of tri-calcium phosphate [Ca₃(PO₄)₂], heat-treated ball-milled clam seashell, and demineralized water are heat-treated at several temperatures (700 °C, 800 °C, 900 °C, 1000 °C, and 1100 °C) for various time periods (1 h, 2 h, and 3 h) to perform the hydrothermal reactions. The phases and microstructure of the solid-state reaction products are analyzed through X-ray diffraction (XRD) method and field emission scanning electron microscopy (FESEM) respectively. The crystallite size of all the synthesized powders is calculated by using Scherrer's model. Mainly HA phase is obtained in all the different reaction products. However, these HAs are found to be non-stoichiometric in nature. As per the literature, non-stoichiometric HA is a more biologically active material compared to the stoichiometric one. Almost pure HA is formed with any selected reaction temperature applied for 2 h time duration. The crystallinity and Ca/P ratio of the synthesized pure HA are estimated by using standard model and energy-dispersive X-ray spectroscopy (EDS) analysis, respectively. The highest amount of near stoichiometric crystalline HA has been obtained at 900 °C of reaction temperature applied for 2 h time duration. With raising reaction temperature, the grain size of pure HA is found to be increased. Needle/rod shaped nano grains are noticed to form at lower reaction temperature whereas; beyond 1000 ^oC of temperature globular/spherical shaped grains are also observed to form. At 3 h reaction time agglomeration of grains is found to occur in all the synthesized powders.     

非饱和残积土土-水特性研究及基质吸力估算

残积土在我国南方分布十分广泛,是工程建设及地质灾害评估中主要遇到的土体之一。非饱和状态下,残积土边坡土体的工程性质不仅取决于土的组成、结构和应力状态,还与土中的吸力密切相关;土-水特征曲线表达了土体中含水量与吸力的关系,是非饱和土研究的重要内容之一。选取福建省有典型代表的凝灰质砂砾岩残积土、凝灰岩残积土以及花岗斑岩残积土3种类型土作为试验土样,测定土样完整的脱湿、吸湿循环过程的土-水特征曲线。鉴于基质吸力测量困难,在Barden非饱和土分类方法的基础上,通过分析具有实际工程意义的含水量情况(饱和度介于50%~90%),总结出的利用饱和度预测基质吸力的简易方法具有针对性和实用性。     

水下自激脉冲射流喷嘴的吸气性能试验研究

运用自行研制的试验装置对水下不同结构参数的自激吸气脉冲射流喷嘴的吸气性能进行试验,研究了喷嘴的上下喷嘴直径、腔径和腔长等不同的组合配比对喷嘴吸气量的影响,以及喷嘴吸气量对喷嘴冲击性能的影响。结果表明:喷嘴吸气是提高水下自激脉冲射流冲击性能的有效途径,喷嘴的相对冲击力随着喷嘴吸气量的增加而提高;在较优的喷嘴结构参数配比范围内,喷嘴的吸气比率最大;最佳吸气比率的喷嘴面积比、相对腔长和相对腔径配比范围分别为3.5~4.0、8~9、11~12.5。     

不同初始缝高比楔入劈拉试件断裂试验研究

为研究初始缝高比对混凝土断裂性能的影响,设计4组共32个不同初始缝高比的试件进行楔入劈拉试验。测定试件断裂过程中的荷载、裂缝张口位移、混凝土应变等参数的特征值及全过程曲线。以双K断裂理论为基础,计算不同初始缝髙比试件的有效裂缝长度a_c、起裂断裂韧度Kⁱⁿⁱ_IC和失稳断裂韧度K^un_IC等断裂参数。试验结果表明:有效裂缝长度a_c随缝高比的增大而增大,裂缝亚临界扩展量Δa_c随缝高比的增大而减小;起裂断裂韧度不受初始缝高比的影响,失稳断裂韧度随缝高比的减少有所增大,当a₀/D≥0.5时,为一常数。