Phosphoproteome Profiling of the Receptor Tyrosine Kinase MuSK Identifies Tyrosine Phosphorylation of Rab GTPases

Muscle-specific receptor tyrosine kinase (MuSK) agonist antibodies were developed 2 decades ago to explore the benefits of receptor activation at the neuromuscular junction. Unlike agrin, the endogenous agonist of MuSK, agonist antibodies function independently of its coreceptor low-density lipoprotein receptor–related protein 4 to delay the onset of muscle denervation in mouse models of ALS. Here, we performed dose–response and time-course experiments on myotubes to systematically compare site-specific phosphorylation downstream of each agonist. Remarkably, both agonists elicited similar intracellular responses at known and newly identified MuSK signaling components. Among these was inducible tyrosine phosphorylation of multiple Rab GTPases that was blocked by MuSK inhibition. Importantly, mutation of this site in Rab10 disrupts association with its effector proteins, molecule interacting with CasL 1/3. Together, these data provide in-depth characterization of MuSK signaling, describe two novel MuSK inhibitors, and expose phosphorylation of Rab GTPases downstream of receptor tyrosine kinase activation in myotubes.     

似鳡属的系统地位及种的分化(鲤形目:鲤科)

似鳡属(Luciocyprinus Vaillant)是鲤科鱼类中属于鲃系(陈湘粦等,1984)的一个属,下咽齿3行,臀鳍无硬刺,具分枝鳍条5根。过去只记载一个种,外形很像鳡鱼,是由于摄食习性相同而导致的趋同现象(林人端,1981),故称似鳡,在广西俗称墨线鳡,云南俗称杆条鱼。分布于西江水系,包括云南中南部的湖泊,与鳡鱼分布于同一水系,但各占一定的水域,互不重叠。 关于似鳡的拉丁名称,惯用Fustis vivus Lin,是林书颜1932年定的新属新种,     

A BC200-derived element and Z-DNA as structural markers in annexin I genes: Relevance to Alu evolution and annexin tetrad formation

We have identified two types of structural elements in genomic DNA for annexin I that provide physical evidence of genetic events leading to conserved changes in gene structure. The sequence upstream of the transcribed region in human annexin I contained a rare, Alu-like repetitive element with flanking direct repeats, probably derived from the active BC200 gene via germline retroposition. Nucleotide substitutions in this BC200 insert relative to the 7SL gene and its absence in rodent annexins I identified it as a recent primate pseudogene. Phylogenetic analysis showed that the BC200 gene represents a new clade of primate Alu evolution that branched near the time of appearance of the progenitor to the free left Alu monomer, FLAM-C. Separate analysis identified a Z-DNA motif in pigeon annexin I intron 7 that may represent the vestigial recombination site involved in primordial assembly of the annexin tetrad. These distinct structural features in annexin I genes provide insight into the evolution of Alu repeats and the mechanism of annexin tetrad formation.     

广东滩涂经济鱼类寄生吸虫──Ⅲ、单孔科、单脏科和八睾科吸虫的研究(复殖目)

本文对广东滩涂经济鱼类寄生复殖吸虫中的单孔科ＨａｐｌｏｐｏｒｉｄａｅＮｉｃｏｌｌ,１９１４,单胜科ＨａｐｌｏｓｐｌａｎｃｈｎｉｄａｅＰｏｃｈｅ,１９２６和八睾科ＯｃｔｏｔｅｓｔｉｄａｅＹａｍａｇｕｔｉ,１９７１吸虫进行研究,其中长尾亚科Ｅｌｏｎａｉｎｕｒｉｎａｅ和鲻长尾吸虫Ｅｌｏｎｇｉｎｕｒｕｓｍｕｕｇｉｌｕｓ分别作为单孔科的新亚科和新属新种;雄囊新单脏吸虫Ｎｅｏｈａｐｌｏｓｐｌａｎｃｈｎｕｓｃｉｒｒｕｓａｃｉ作为单脏科的新属新种;天竺鲷八睾吸虫Ｏｃｔｏｔｅｓｔｉｓａｐｏｇｏｎｉ作为八睾科、八睾吸虫属Ｏｃｔｏｔｅｓｔｉｓ（Ｗａｎｇ,１９６３）Ｙａｍａｇｕｔｉ,１９５１的新种。     

Angelman syndrome and severe infections in a patient with de novo 15q11.2–q13.1 deletion and maternally inherited 2q21.3 microdeletion

Angelman syndrome is a neurodevelopmental disorder characterized by mental retardation, severe speech disorder, facial dysmorphism, secondary microcephaly, ataxia, seizures, and abnormal behaviors such as easily provoked laughter. It is most frequently caused by a de novo maternal deletion of chromosome 15q11–q13 (about 70–90%), but can also be caused by paternal uniparental disomy of chromosome 15q11–q13 (3–7%), an imprinting defect (2–4%) or in mutations in the ubiquitin protein ligase E3A gene UBE3A mostly leading to frame shift mutation. In addition, for patients with overlapping clinical features (Angelman-like syndrome), mutations in methyl-CpG binding protein 2 gene MECP2 and cyclin-dependent kinase-like 5 gene CDKL5 as well as a microdeletion of 2q23.1 including the methyl-CpG binding domain protein 5 gene MBD5 have been described. Here, we describe a patient who carries a de novo 5 Mb-deletion of chromosome 15q11.2–q13.1 known to be associated with Angelman syndrome and a further, maternally inherited deletion 2q21.3 (~ 364 kb) of unknown significance. In addition to classic features of Angelman syndrome, she presented with severe infections in the first year of life, a symptom that has not been described in patients with Angelman syndrome. The 15q11.2–q13.1 deletion contains genes critical for Prader–Willi syndrome, the Angelman syndrome causing genes UBE3A and ATP10A/C, and several non-imprinted genes: GABRB3 and GABRA5 (both encoding subunits of GABA A receptor), GOLGA6L2, HERC2 and OCA2 (associated with oculocutaneous albinism II). The deletion 2q21.3 includes exons of the genes RAB3GAP1 (associated with Warburg Micro syndrome) and ZRANB3 (not disease-associated). Despite the normal phenotype of the mother, the relevance of the 2q21.3 microdeletion for the phenotype of the patient cannot be excluded, and further case reports will need to address this point.     

A new subfamily and species of Ostracoda (Cylindroleberididae,Myodocopa) from the Chatham Rise (New Zealand)

Abstract

The second species of the genus, Macroasteropteron chathamensis sp. nov. is described in the present paper. It was collected from 1000 m depth during the New Zealand national biodiversity programme Ocean Survey 20/20 to the Chatham Rise and the Challenger Plateau. To accommodate this genus, a new subfamily Macroasteropteroninae is described herein. It is defined by the following autapomorphies: locking system on the shell; very small second segment on the second antenna (bearing no dorsal bristles); square shaped third and fourth segments on the same appendage; absence of dorsal bristles on the third segment of the male clasping organ; reverse position of the alpha and beta bristles on the maxillula; almost square shaped skirt on the sixth limb; and a bulbous terminal part of the seventh limb, which, in addition, does not have any bell-bearing bristles. A key to the four subfamilies of Cylindroleberididae is provided.     

Stability of ultramer as copy number standards in real-time PCR

Since commercial copy number standards are not always available for real-time PCR, alternative sources of DNA are used. Unfortunately, stored genomic DNA or PCR amplicon has been shown to be unstable, resulting in variable copy number. More recently, the use of ultramer as copy number standard has been reported. However, there is little information on the stability of ultramer under different storage conditions. Thus the aim of this study was to determine the stability of ultramer as copy number standard under different storage conditions using different mixing methods. We found that ultramer copy number was not affected by storage at either 4 °C or − 20 °C over a period of 30 days. Furthermore, the method of mixing the ultramer did not appear to contribute to variability in results. Irrespective of storage temperature or mixing method, there was less than 5% variance in Ct value over a period of 30 days. A duplicate set of standards costs approximately $0.01. Therefore, the use of ultramer as copy number standards in real-time PCR, is cost effective and convenient.     

Different coexpressions of arthritis-relevant genes between different body organs and different brain regions in the normal mouse population

Structural changes in different parts of the brain in rheumatoid arthritis (RA) patients have been reported. RA is not regarded as a brain disease. Body organs such as spleen and lung produce RA-relevant genes. We hypothesized that the structural changes in the brain are caused by changes of gene expression in body organs. Changes in different parts of the brain may be affected by altered gene expressions in different body organs. This study explored whether an association between gene expressions of an organ or a body part varies in different brain structures. By examining the association of the 10 most altered genes from a mouse model of spontaneous arthritis in a normal mouse population, we found two groups of gene expression patterns between five brain structures and spleen. The correlation patterns between the prefrontal cortex, nucleus accumbens, and spleen were similar, while the associations between the other three parts of the brain and spleen showed a different pattern. Among overall patterns of the associations between body organs and brain structures, spleen and lung had a similar pattern, and patterns for kidney and liver were similar. Analysis of the five additional known arthritis-relevant genes produced similar results. Analysis of 10 nonrelevant-arthritis genes did not result in a strong association of gene expression or clearly segregated patterns. Our data suggest that abnormal gene expressions in different diseased body organs may influence structural changes in different brain parts.     

The first Praesiricidae (Hymenoptera) from Northeast China

A new subfamily Rudisiricinae Gao, Rasnitsyn, Ren & Shih, n. subfam. and a new genus Rudisiricius Gao, Rasnitsyn, Ren & Shih, n. gen. with three new species R. belli Gao, Rasnitsyn, Ren & Shih n. sp., R. crassinodus Gao, Rasnitsyn, Ren & Shih, n. sp., and R. celsus Gao, Rasnitsyn, Ren & Shih, n. sp. are described and illustrated from the family Praesiricidae. The type specimens were collected from the Late Jurassic to Early Cretaceous Yixian Formation, northeastern China. The new subfamily also includes Aulidontes Rasnitsyn from the Upper Jurassic of Karatau in Kazakhstan. This is the first record of Praesiricidae in China. These well-preserved nearly-complete new fossils reported here provide additional material and structure characters about this family, which helps filling some gap in the evolution of Lower Hymenoptera.     

Activation of TRPV4 channel in pancreatic INS-1E beta cells enhances glucose-stimulated insulin secretion via calcium-dependent mechanisms

Transient receptor potential channel vanilloid type 4 (TRPV4) is a Ca²⁺- and Mg²⁺-permeable cation channel that influences oxidative metabolism and insulin sensitivity. The role of TRPV4 in pancreatic beta cells is largely unknown. Here, we characterize the role of TRPV4 in controlling intracellular Ca²⁺ and insulin secretion in INS-1E beta cells. Osmotic, thermal or pharmacological activation of TRPV4 caused a rapid rise of intracellular Ca²⁺ and enhanced glucose-stimulated insulin secretion. In the presence of the TRPV channel blocker ruthenium red (RuR) or after suppression of TRPV4 protein production, TRPV4 activators failed to increase [Ca²⁺]_i and insulin secretion in INS-1E cells.