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Damjana Kastelic Nicolas Soler Radovan Komel Denis Pompon 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
A large fraction of camelid (camels and llamas) antibodies is composed of heavy chain-only homodimers, able to recognise antigens with their variable domain. Events in somatic assembly and maturation of antibodies such as hypermutations and rearrangement of variable loops (CDRs — complementary determining regions) and selection among a wide range of framework variants are generally considered to be random processes.Methods
An original algorithmic approach (Global Sequence Signature—GSS) was developed, able to take into account multiple functional and/or local sequence properties to detect scattered evolutionary constraints into sequences.Results
Using the GSS approach, we show that the length of the main hypervariable loop (CDR3) is linked to the nature of 19 surrounding residues on the scaffold. Surprisingly, the relation between CDR3 size and scaffold residues strongly depends on the considered species, illustrating either significant differences in selection mechanisms or functional constraints during antibody maturation.Conclusions
Combined with the statistical coupling analysis (SCA) approach at the level of scaffold residues, this study has unravelled a robust interaction network on antibody structure surrounding the CDR3 loop.General significance
In addition to the general applicability of the GSS algorithm, which can bring together functional and sequence data to locate hot spots of constrained evolution, the relationship between CDR3 and scaffold discussed here should be taken into account in protein engineering when designing antibody libraries. 相似文献174.
目的:研究纳米卟啉金属有机骨架(NPMOF)对斑马鱼幼鱼神经系统发育的作用。方法:斑马鱼胚胎在发育6 h(hpf)后随机分为两组:对照组(n=500)和暴露组(n=500),对照组斑马鱼孵化于E3溶液中,暴露组于100 mg/L的NPMOF-E3溶液中,持续暴露至28、48、72、96或120 hpf。以20条斑马鱼为一批,在28、48、72、96和120 hpf分别提取3批实验组和对照组的总RNA用于RT-PCR;在120 hpf,实验组和对照组分别取20条PTU处理过的斑马鱼用于整体胚胎原位杂交,同样是在120 hpf,每组取150条用于免疫荧光染色,30条用于行为学测试。NPMOF的形状和尺寸用透射电镜测定,其光学特性由紫外分光光度计和荧光光谱仪测定;通过免疫荧光、整体胚胎原位杂交和RT-PCR方法检测各类神经细胞的发育;行为学测试用来监测斑马鱼运动状态的改变。结果:与正常组比较,NPMOF暴露组中神经发育相关基因的表达明显升高(P<0.05),müller细胞和星形胶质细胞的数量明显增加(P<0.05),神经元和少突胶质细胞的分布与形态未显示出差异;行为学测试中,斑马鱼的总运动距离、快速运动时间和运动速度的值显著增加(P<0.05),总静止时间明显降低(P<0.05)。结论:100 mg/L NPMOF溶液的持续暴露对斑马鱼神经系统发育,特别是视网膜中müller细胞和脑中星形胶质细胞的发育有促进作用。 相似文献
175.
Daniel R. Prez Claudio Pilustrelli Fernando M. Farinaccio Guillermo Sabino James Aronson 《Restoration Ecology》2020,28(Z1):A44-A53
Field data and unmanned aerial vehicles, also known as drones, were used to analyze a long‐term experiment in a severely degraded area of the “Monte,” one of the most arid and degraded biomes in Argentina. Field methods and drone orthoimages obtained from flights of a quadcopter at 20 and 40 m were used to compare plantation plots versus natural recovery on scarified sites, and the field performance of six putative framework species under four different treatments was evaluated. After 5 years of recovery in soils with almost no organic matter and mean annual rainfall averaging 145 mm, plantation plots had high survival rates (>65%) for all species as determined through both field survey and drone imagery. Three species were planted with a greater number of seedlings due to their availability in nurseries. For these species experimental treatments were studied statistically. Independently of treatment applied (control; 1/2 L hydrogel; 1 L hydrogel; 1 L of hydrogel + 1/2 kg of organic compost), highest survival rates were found for P. flexuosa var. depressa (88% ± 14.8) and A. lampa (84% ± 14.8). Drone images and field data both showed that these two putative framework species had the highest plant cover. In sharp contrast, mechanical scarification without planting or other treatments induced very low recovery (<2%). We demonstrate that drone imagery provides a new and very valuable tool for evaluating and monitoring restorative interventions in drylands. 相似文献
176.
Taoli Jiang Pingge He Guoxu Wang Yang Shen Ce‐Wen Nan Li‐Zhen Fan 《Liver Transplantation》2020,10(12)
Thin solid‐state electrolytes with nonflammability, high ionic conductivity, low interfacial resistance, and good processability are urgently required for next‐generation safe, high energy density lithium metal batteries. Here, a 3D Li6.75La3Zr1.75Ta0.25O12 (LLZTO) self‐supporting framework interconnected by polytetrafluoroethylene (PTFE) binder is prepared through a simple grinding method without any solvent. Subsequently, a garnet‐based composite electrolyte is achieved through filling the flexible 3D LLZTO framework with a succinonitrile solid electrolyte. Due to the high content of garnet ceramic (80.4 wt%) and high heat‐resistance of the PTFE binder, such a composite electrolyte film with nonflammability and high processability exhibits a wide electrochemical window of 4.8 V versus Li/Li+ and high ionic transference number of 0.53. The continuous Li+ transfer channels between interconnected LLZTO particles and succinonitrile, and the soft electrolyte/electrode interface jointly contribute to a high ambient‐temperature ionic conductivity of 1.2 × 10?4 S cm?1 and excellent long‐term stability of the Li symmetric battery (stable at a current density of 0.1 mA cm?2 for over 500 h). Furthermore, as‐prepared LiFePO4|Li and LiNi0.5Mn0.3Co0.2O2|Li batteries based on the thin composite electrolyte exhibit high discharge specific capacities of 153 and 158 mAh g?1 respectively, and desirable cyclic stabilities at room temperature. 相似文献
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Brouillard JN Günther S Varma AK Gryski I Herfst CA Rahman AK Leung DY Schlievert PM Madrenas J Sundberg EJ McCormick JK 《Journal of molecular biology》2007,367(4):925-934
Superantigens (SAgs) are potent microbial toxins that bind simultaneously to T cell receptors (TCRs) and class II major histocompatibility complex molecules, resulting in the activation and expansion of large T cell subsets and the onset of numerous human diseases. Within the bacterial SAg family, streptococcal pyrogenic exotoxin I (SpeI) has been classified as belonging to the group V SAg subclass, which are characterized by a unique, relatively conserved ∼15 amino acid extension (amino acid residues 154 to 170 in SpeI; herein referred to as the α3-β8 loop), absent in SAg groups I through IV. Here, we report the crystal structure of SpeI at 1.56 Å resolution. Although the α3-β8 loop in SpeI is several residues shorter than that of another group V SAg, staphylococcal enterotoxin serotype I, the C-terminal portions of these loops, which are located adjacent to the putative TCR binding site, are structurally similar. Mutagenesis and subsequent functional analysis of SpeI indicates that TCR β-chains are likely engaged in a similar general orientation as other characterized SAgs. We show, however, that the α3-β8 loop length, and the presence of key glycine residues, are necessary for optimal activation of T cells. Based on Vβ-skewing analysis of human T cells activated with SpeI and structural models, we propose that the α3-β8 loop is positioned to form productive intermolecular contacts with the TCR β-chain, likely in framework region 3, and that these contacts are required for optimal TCR recognition by SpeI, and likely all other group V SAgs. 相似文献