Ube3a,the E3 ubiquitin ligase causing Angelman syndrome and linked to autism,regulates protein homeostasis through the proteasomal shuttle Rpn10

Ubiquitination, the covalent attachment of ubiquitin to a target protein, regulates most cellular processes and is involved in several neurological disorders. In particular, Angelman syndrome and one of the most common genomic forms of autism, dup15q, are caused respectively by lack of or excess of UBE3A, a ubiquitin E3 ligase. Its Drosophila orthologue, Ube3a, is also active during brain development. We have now devised a protocol to screen for substrates of this particular ubiquitin ligase. In a neuronal cell system, we find direct ubiquitination by Ube3a of three proteasome-related proteins Rpn10, Uch-L5, and CG8209, as well as of the ribosomal protein Rps10b. Only one of these, Rpn10, is targeted for degradation upon ubiquitination by Ube3a, indicating that degradation might not be the only effect of Ube3a on its substrates. Furthermore, we report the genetic interaction in vivo between Ube3a and the C-terminal part of Rpn10. Overexpression of these proteins leads to an enhanced accumulation of ubiquitinated proteins, further supporting the biochemical evidence of interaction obtained in neuronal cells.     

Competence to replicate in the unfertilized egg is conferred by Cdc6 during meiotic maturation

Meiotic maturation, the final step of oogenesis, is a crucial stage of development in which an immature oocyte becomes a fertilizable egg. In Xenopus, the ability to replicate DNA is acquired during maturation at breakdown of the nuclear envelope by translation of a DNA synthesis inducer that is not present in the oocyte. Here we identify Cdc6, which is essential for recruiting the minichromosome maintenance (MCM) helicase to the pre-replication complex, as this inducer of DNA synthesis. We show that maternal cdc6 mRNA but not protein is stored in the oocyte. Cdc6 protein is synthesized during maturation, but this process can be blocked by degrading the maternal cdc6 mRNA by oligonucleotide antisense injections or by translation inhibition. Rescue experiments using recombinant Cdc6 protein show that Cdc6 is the only missing replication factor whose translation is necessary and sufficient to confer DNA replication competence to the egg before fertilization. The licence to replicate is given by Cdc6 at the end of meiosis I, but the cytostatic factor (CSF) pathway, which maintains large amounts of active Cdc2/Cyclin B2, prevents the entry into S phase until fertilization.     

烧结?Al?B4C 复合材料的往复滑动磨损性能

采用粉末冶金法制备了不同 B₄C 含量（1wt%、6wt%、15wt% 和 30wt%）的碳化硼增强铝基复合材料（Al?B₄C）,并研究了 B4C 含量对其力学性能和摩擦学行为的影响。在7 N载荷下, Al?30B₄C 复合材料的密度最高 (~2.54 g/cm3)、孔隙率最低 (4%)、维氏硬度最高 (HV ~75)、重量损失最低 (0.4 mg) 和比磨损率最低 (0.00042 mm3/ (N·m)),与纯铝相比,硬度提高167%,失重降低75.8%,比磨损率降低76.7%。此外,磨损表面的扫描电镜图像显示,Al?B₄C复合材料在7 N载荷下的最窄磨损槽为0.85 mm,主要磨损机制为磨粒磨损机制。根据摩擦分析,表面之间的摩擦系数随着碳化硼含量的增加和外加载荷的减少而增加。总之,就 Al?B₄C 复合材料的摩擦学和力学性能而言,B₄C 是一种有效的增强材料。     

A collision in 2009 as the origin of the debris trail of asteroid P/2010 A2

The peculiar object P/2010?A2 was discovered in January 2010 and given a cometary designation because of the presence of a trail of material, although there was no central condensation or coma. The appearance of this object, in an asteroidal orbit (small eccentricity and inclination) in the inner main asteroid belt attracted attention as a potential new member of the recently recognized class of main-belt comets. If confirmed, this new object would expand the range in heliocentric distance over which main-belt comets are found. Here we report observations of P/2010?A2 by the Rosetta spacecraft. We conclude that the trail arose from a single event, rather than a period of cometary activity, in agreement with independent results. The trail is made up of relatively large particles of millimetre to centimetre size that remain close to the parent asteroid. The shape of the trail can be explained by an initial impact ejecting large clumps of debris that disintegrated and dispersed almost immediately. We determine that this was an asteroid collision that occurred around 10 February 2009.     

Origin of AIDS: contaminated polio vaccine theory refuted

Despite strong evidence to the contrary, speculation continues that the AIDS virus, human immunodeficiency virus type 1 (HIV-1), may have crossed into humans as a result of contamination of the oral polio vaccine (OPV). This 'OPV/AIDS theory' claims that chimpanzees from the vicinity of Stanleyville--now Kisangani in the Democratic Republic of Congo--were the source of a simian immunodeficiency virus (SIVcpz) that was transmitted to humans when chimpanzee tissues were allegedly used in the preparation of OPV. Here we show that SIVcpz is indeed endemic in wild chimpanzees of this region but that the circulating virus is phylogenetically distinct from all strains of HIV-1, providing direct evidence that these chimpanzees were not the source of the human AIDS pandemic.     

The effect of early weaning on spermiogenesis in adult rats

Zusammenfassung Junge, vorzeitig (18 Tage nach der Geburt entwöhnte Ratten) zeigen im Alter von 12 Monaten Schädigungen im spermiogenen Hodenepithel. 12 Tage später entwöhnte Ratten entwickeln sich normal. Die beobachteten Schädigungen treten im Alter von 6 Monaten noch nicht auf.     

‘Insulin-like’ action of an oxytocin analogue lacking a disulphide group,and of a cystathionine peptide related to a sequence of insulin,on rat epididymal adipose tissue in vitro

Zusammenfassung Es wird mittels synthetischer Peptide (Ib, II) bewiesen, dass eine Disulphidgruppe für die « insulinähnliche » Wirkung von mit dem Oxytocin verwandten Peptiden am Fettgewebe der Rattenepididymis nicht notwendig ist. Somit wird ein von Disulphidaustausch abhängiger Wirkungsmechanismus ausgeschlossen.