c-Src is a PDZ interaction partner and substrate of the E3 ubiquitin ligase Ligand-of-Numb protein X1

The very C-terminus of c-Src is a ligand for PDZ domains. In a screen for PDZ domains that interact with c-Src, we identified one of the PDZ domains of the Ligand-of-Numb protein X1 (LNX1), a multiple PDZ domain scaffold and RING type E3 ubiquitin ligase. We demonstrate that the interaction of c-Src with LNX1 depends on the C-terminal PDZ ligand of c-Src. Furthermore, we show that c-Src phosphorylates LNX1. Moreover, c-Src itself is ubiquitinated by LNX1, suggesting an interdependent regulation of c-Src and LNX1.     

耳穴埋豆联合针刺对脑梗死患者睡眠质量及吞咽功能的影响

摘要 目的：探讨耳穴埋豆联合针刺对脑梗死患者睡眠质量及吞咽功能的影响。方法：选取2016年3月2日至2021年3月2日于我院进行脑梗死治疗的80例患者,将其随机分为观察组（n=40）和对照组（n=40）,观察组采用耳穴埋豆联合针刺治疗干预,对照组采用常规治疗,对比两组患者匹兹堡睡眠质量指数问卷（Pitsburgh sleep quality index,PSQI）评分和睡眠状况自评量表（Self-Rating Scale of Sleep,SRSS）评分、渗透-误吸量表（Penetration-aspiration scale,PAS）评分、吞咽功能治疗有效率、治疗满意度。结果：治疗干预后,观察组患者的PSQI评分及SRSS评分明显优于对照组,差异有统计学意义（P<0.05）;治疗前,比较两组患者3种食团PAS评分,差异均无统计学意义（P>0.05）。治疗后,比较两组患者3种食团PAS评分,均较治疗前明显下降,差异有统计学意义（P<0.05）。观察组5 mL水、10 mL水PAS评分明显低于对照组（P<0.05）,而比较两组患者5 mL布丁样食物PSA评分,差异无统计学意义（P>0.05）;观察组患者吞咽障碍经治疗后总有效率为90 %;对照组患者吞咽障碍经治疗后总有效率为70 %。差异有统计学意义（P<0.05）;观察组满意度明显高于对照组（P<0.05）。结论：耳穴埋豆联合针刺治疗方法应用于脑梗死患者,可有效改善睡眠质量,提升患者吞咽功能,提高吞咽障碍治疗率,患者满意度提高,可应用于临床。     

四川贡嘎山国家级自然保护区鸟兽多样性

四川贡嘎山国家级自然保护区位于全球生物多样性热点地区之一的横断山区, 是我国生物多样性保护优先区。本文利用红外相机影像和已发表文献对该保护区的大中型兽类和地面活动鸟类进行编目并提出未来监测建议。2011-2018年在97个1 km × 1 km的网格安放红外相机, 累计39,881个相机日, 获得独立有效照片20,932张, 其中野生兽类16,244张, 鸟类2,775张, 牲畜1,737张, 人176张。鉴定出野生兽类30种, 另有文献报道4种和观察3种, 分属于5目15科; 鸟类78种, 分属于9目22科; 牲畜6种。包括12种国家I级和28种国家II级重点保护野生动物; 被CITES附录I收录的有11种, 附录II收录的有12种。被IUCN红色名录评估为濒危(EN)和易危(VU)等级的分别有3种和8种。被《中国脊椎动物红色名录》评估为极危(CR)、濒危和易危等级的分别有5、5和11种。相对多度指数(relative abundance index, RAI)排名前三的兽类是毛冠鹿(Elaphodus cephalophus, 147.39)、水鹿(Rusa unicolor, 66.10)、野猪(Sus scrofa, 36.03); 鸟类是血雉(Ithaginis cruentus, 14.64)、白马鸡(Crossoptilon crossoptilon, 10.43)、大噪鹛(Garrulax maximus, 8.05)。阔叶林、针阔混交林、高山灌丛草甸和高山流石滩是调查薄弱生境, 后期应开展重点调查, 以厘清本区域大中型兽类资源。     

Genetic structure and domestication footprints of the tusk,coat color,and ear morphology in East Chinese pigs

The domestication and artificial selection of wild boars have led to dramatic morphological and behavioral changes, especially in East Chinese (ECN) pigs. Here, we provide insights into the population structure and current genetic diversity of representative ECN pig breeds. We identify a 500-kb region containing six tooth development-relevant genes with almost completely different haplotypes between ECN pigs and Chinese wild boars or European domestic pigs. Notably, the c.195A>G missense mutation in exon 2 of AMBN may cause alterations in its protein structure associated with tusk degradation in ECN pigs. In addition, ESR1 may play an important role in the reproductive performance of ECN pigs. A major haplotype of the large lop ear-related MSRB3 gene and eight alleles in the deafness-related GRM7 gene may affect ear morphology and hearing in ECN pigs. Interestingly, we find that the two-end black (TEB) coat color in Jinhua pigs is most likely caused by EDNRB with genetic mechanisms different from other Chinese TEB pigs. This study identifies key loci that may be artificially selected in Chinese native pigs related to the tusk, coat color, and ear morphology, thus providing new insights into the genetic mechanisms of domesticated pigs.     

The PDZ-GEF Gef26 regulates synapse development and function via FasII and Rap1 at the Drosophila neuromuscular junction

Guanine nucleotide exchange factors (GEFs) are essential for small G proteins to activate their downstream signaling pathways, which are involved in morphogenesis, cell adhesion, and migration. Mutants of Gef26, a PDZ-GEF (PDZ domain-containing guanine nucleotide exchange factor) in Drosophila, exhibit strong defects in wings, eyes, and the reproductive and nervous systems. However, the precise roles of Gef26 in development remain unclear. In the present study, we analyzed the role of Gef26 in synaptic development and function. We identified significant decreases in bouton number and branch length at larval neuromuscular junctions (NMJs) in Gef26 mutants, and these defects were fully rescued by restoring Gef26 expression, indicating that Gef26 plays an important role in NMJ morphogenesis. In addition to the observed defects in NMJ morphology, electrophysiological analyses revealed functional defects at NMJs, and locomotor deficiency appeared in Gef26 mutant larvae. Furthermore, Gef26 regulated NMJ morphogenesis by regulating the level of synaptic Fasciclin II (FasII), a well-studied cell adhesion molecule that functions in NMJ development and remodeling. Finally, our data demonstrate that Gef26-specific small G protein Rap1 worked downstream of Gef26 to regulate the level of FasII at NMJs, possibly through a βPS integrin-mediated signaling pathway. Taken together, our findings define a novel role of Gef26 in regulating NMJ development and function.     

Spatial distribution and landscape associations of large-antlered deer

For more than a century, the Boone and Crockett Club has kept records of harvest locations for 38 categories of North American big game, which includes measurement details and sizes of enduring characteristics (e.g., antlers, skulls, horns). All white-tailed deer (Odocoileus virginianus) entered in the Club records (i.e., record deer) have large antlers because the measurements must meet or exceed a minimum size to qualify for entry. We used the records from the Club to test the hypothesis that the spatial distribution in the harvest of record deer was related to the number of antlered deer harvested, variations in land productivity, soil mineral content, and attributes of land cover for 9 states in the midwestern United States. We used a Bayesian theoretical framework to develop a spatial model that examined the influence of explanatory variables on the number of record deer harvested in each county. In our study area, 3,658 record deer were harvested in 692 of the 856 counties (80.8%). More record deer were harvested in counties that had more high-contrast edges, less contiguous land cover, and greater variation in soil productivity. These results provide information for managers and hunters to better understand the spatial distribution of record deer and factors that are correlated with their distribution. © 2019 The Wildlife Society.     

Effect of sterol structure on ordered membrane domain (raft) stability in symmetric and asymmetric vesicles

Sterol structure influences liquid ordered domains in membranes, and the dependence of biological functions on sterol structure can help identify processes dependent on ordered domains. In this study we compared the effect of sterol structure on ordered domain formation in symmetric vesicles composed of mixtures of sphingomyelin, 1, 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and cholesterol, and in asymmetric vesicles in which sphingomyelin was introduced into the outer leaflet of vesicles composed of DOPC and cholesterol. In most cases, sterol behavior was similar in symmetric and asymmetric vesicles, with ordered domains most strongly stabilized by 7-dehydrocholesterol (7DHC) and cholesterol, stabilized to a moderate degree by lanosterol, epicholesterol and desmosterol, and very little if at all by 4-cholesten-3-one. However, in asymmetric vesicles desmosterol stabilized ordered domain almost as well as cholesterol, and to a much greater degree than epicholesterol, so that the ability to support ordered domains decreased in the order 7-DHC > cholesterol > desmosterol > lanosterol > epicholesterol > 4-cholesten-3-one. This contrasts with values for intermediate stabilizing sterols in symmetric vesicles in which the ranking was cholesterol > lanosterol ~ desmosterol ~ epicholesterol or prior studies in which the ranking was cholesterol ~ epicholesterol > lanosterol ~ desmosterol. The reasons for these differences are discussed. Based on these results, we re-evaluated our prior studies in cells and conclude that endocytosis levels and bacterial uptake are even more closely correlated with the ability of sterols to form ordered domains than previously thought, and do not necessarily require that a sterol have a 3β-OH group.     

Interaction of sauger Sander canadensis and walleye Sander vitreus in a large,shallow northern river

The objectives of this study were to: (1) determine the relative abundance of sauger Sander canadensis and walleye S. vitreus within the Rainy River using a standardized index netting technique; (2) assess the life-history characteristics of the two species in a northern river; (3) examine the spatial distribution of the two species; (4) assess year-class synchrony. At a larger scale, relative abundance of S. canadensis and S. vitreus were similar among sections of the river. However, at a finer scale, S. canadensis were the dominant species over more area (24%) of the river than S. vitreus (12%). Life-history traits for both species were within the range reported for North American. Mortality rates were similar, suggesting that anglers were not affecting one species more than the other. Year-class strengths were not synchronous between S. canadensis and S. vitreus (r = 0.07). There was evidence of S. canadensis potentially outcompeting S. vitreus with a strong year class of S. canadensis followed by a very weak class of S. vitreus. Additionally, S. canadensis were larger than S. vitreus in most sections of the river when adjusted for mean size. However, the potential interspecific competition was not to the exclusion of S. vitreus. Turbidity was probably the factor that enable S. canadensis to survive sympatrically with S. vitreus given their inability to segregate by depth within the river.     

Lateral hydrological connectivity differentially affects the community characteristics of multiple groups of aquatic invertebrates in tropical wetland pans in South Africa

相似文献   

Immune checkpoint blockade and its combination therapy with small-molecule inhibitors for cancer treatment

Initially understood for its physiological maintenance of self-tolerance, the immune checkpoint molecule has recently been recognized as a promising anti-cancer target. There has been considerable interest in the biology and the action mechanism of the immune checkpoint therapy, and their incorporation with other therapeutic regimens. Recently the small-molecule inhibitor (SMI) has been identified as an attractive combination partner for immune checkpoint inhibitors (ICIs) and is becoming a novel direction for the field of combination drug design. In this review, we provide a systematic discussion of the biology and function of major immune checkpoint molecules, and their interactions with corresponding targeting agents. With both preclinical studies and clinical trials, we especially highlight the ICI + SMI combination, with its recent advances as well as its application challenges.