Implications of the polymorphism of HLA-G on its function,regulation, evolution and disease association

The HLA-G gene displays several peculiarities that are distinct from those of classical HLA class I genes. The unique structure of the HLA-G molecule permits a restricted peptide presentation and allows the modulation of the cells of the immune system. Although polymorphic sites may potentially influence all biological functions of HLA-G, those present at the promoter and 3′ untranslated regions have been particularly studied in experimental and pathological conditions. The relatively low polymorphism observed in the MHC-G coding region both in humans and apes may represent a strong selective pressure for invariance, whereas, in regulatory regions several lines of evidence support the role of balancing selection. Since HLA-G has immunomodulatory properties, the understanding of gene regulation and the role of polymorphic sites on gene function may permit an individualized approach for the future use of HLA-G for therapeutic purposes.     

CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs

Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by recurrent infections of the upper and lower respiratory tract, reduced fertility in males and situs inversus in about 50% of affected individuals (Kartagener syndrome). It is caused by motility defects in the respiratory cilia that are responsible for airway clearance, the flagella that propel sperm cells and the nodal monocilia that determine left-right asymmetry. Recessive mutations that cause PCD have been identified in genes encoding components of the outer dynein arms, radial spokes and cytoplasmic pre-assembly factors of axonemal dyneins, but these mutations account for only about 50% of cases of PCD. We exploited the unique properties of dog populations to positionally clone a new PCD gene, CCDC39. We found that loss-of-function mutations in the human ortholog underlie a substantial fraction of PCD cases with axonemal disorganization and abnormal ciliary beating. Functional analyses indicated that CCDC39 localizes to ciliary axonemes and is essential for assembly of inner dynein arms and the dynein regulatory complex.     

Late middle Eocene epoch of Libya yields earliest known radiation of African anthropoids

Reconstructing the early evolutionary history of anthropoid primates is hindered by a lack of consensus on both the timing and biogeography of anthropoid origins. Some prefer an ancient (Cretaceous) origin for anthropoids in Africa or some other Gondwanan landmass, whereas others advocate a more recent (early Cenozoic) origin for anthropoids in Asia, with subsequent dispersal of one or more early anthropoid taxa to Africa. The oldest undoubted African anthropoid primates described so far are three species of the parapithecid Biretia from the late middle Eocene Bir El Ater locality of Algeria and the late Eocene BQ-2 site in the Fayum region of northern Egypt. Here we report the discovery of the oldest known diverse assemblage of African anthropoids from the late middle Eocene Dur At-Talah escarpment in central Libya. The primate assemblage from Dur At-Talah includes diminutive species pertaining to three higher-level anthropoid clades (Afrotarsiidae, Parapithecidae and Oligopithecidae) as well as a small species of the early strepsirhine primate Karanisia. The high taxonomic diversity of anthropoids at Dur At-Talah indicates either a much longer interval of anthropoid evolution in Africa than is currently documented in the fossil record or the nearly synchronous colonization of Africa by multiple anthropoid clades at some time during the middle Eocene epoch.     

一种新的中空纤维液流场流分离装置及其对葡聚糖保留行为的研究

中空纤维液流场流分离法对高分子和小粒子分离效果好,但目前因所使用的中空纤维均为各实验室自制且分子量阻断值不够小,使该技术的推广应用受到限制.设计了一种新的中空纤维液流场流分离装置,该装置的优越性在于其中空纤维分子量阻断值小,可以用于分离较小分子量的分子;并且中空纤维为商业购买,使得该技术的推广成为可能;该装置易于安装,操作简便.应用它获得了高分子物质葡聚糖的保留,并探讨了液流交汇时间、外场强度、流速和进样量对葡聚糖保留行为的影响.研究结果表明,给予足够的液流交汇时间,足够强的外场,葡聚糖能得到很好的保留.超量进样时,被测葡聚糖的保留时间不变,峰的对称性良好,结果重现性好.     

光学异常透射的微观理论

本文介绍了作者最近在《自然》杂志（Nature,2008,452：728-31）发表的一项解释光学异常透射的微观理论。该理论建立了描述异常透射的一个金属表面等离子体（surface plasmon polariton,SPP）模型,通过比较模型预言的结果和严格求解Maxwell方程组全矢量方法的数值计算结果,发现在可见光及近红外波段,该模型能够定量给出异常透射的所有主要特征,从而验证了该模型的有效性。由于模型中仅保留了SPP而忽略了其它金属表面波,因此能够单独考察SPP在异常透射中的贡献,有助于调和之前不同观点间的争论。同时,由于该模型将二维孔阵列分解为一维孔链的周期组合,然后综合考虑各孔链处SPP的激发及散射过程。因此能够从微观层面分析形成异常透射的物理原因,解释了传统模式展开方法中表面Bloch模式的物理根源,同时能够为相关器件的设计提供理论指导。     

Deficiency of UBR1, a ubiquitin ligase of the N-end rule pathway, causes pancreatic dysfunction, malformations and mental retardation (Johanson-Blizzard syndrome)

Johanson-Blizzard syndrome (OMIM 243800) is an autosomal recessive disorder that includes congenital exocrine pancreatic insufficiency, multiple malformations such as nasal wing aplasia, and frequent mental retardation. We mapped the disease-associated locus to chromosome 15q14-21.1 and identified mutations, mostly truncating ones, in the gene UBR1 in 12 unrelated families with Johanson-Blizzard syndrome. UBR1 encodes one of at least four functionally overlapping E3 ubiquitin ligases of the N-end rule pathway, a conserved proteolytic system whose substrates include proteins with destabilizing N-terminal residues. Pancreas of individuals with Johanson-Blizzard syndrome did not express UBR1 and had intrauterine-onset destructive pancreatitis. In addition, we found that Ubr1(-/-) mice, whose previously reported phenotypes include reduced weight and behavioral abnormalities, had an exocrine pancreatic insufficiency, with impaired stimulus-secretion coupling and increased susceptibility to pancreatic injury. Our findings indicate that deficiency of UBR1 perturbs the pancreas' acinar cells and other organs, presumably owing to metabolic stabilization of specific substrates of the N-end rule pathway.     

Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome

Apoptosis is an evolutionarily conserved cell suicide process executed by cysteine proteases (caspases) and regulated by the opposing factions of the Bcl-2 protein family. Mammalian caspase-9 and its activator Apaf-1 were thought to be essential, because mice lacking either of them display neuronal hyperplasia and their lymphocytes and fibroblasts seem resistant to certain apoptotic stimuli. Because Apaf-1 requires cytochrome c to activate caspase-9, and Bcl-2 prevents mitochondrial cytochrome c release, Bcl-2 is widely believed to inhibit apoptosis by safeguarding mitochondrial membrane integrity. Our results suggest a different, broader role, because Bcl-2 overexpression increased lymphocyte numbers in mice and inhibited many apoptotic stimuli, but the absence of Apaf-1 or caspase-9 did not. Caspase activity was still discernible in cells lacking Apaf-1 or caspase-9, and a potent caspase antagonist both inhibited apoptosis and retarded cytochrome c release. We conclude that Bcl-2 regulates a caspase activation programme independently of the cytochrome c/Apaf-1/caspase-9 'apoptosome', which seems to amplify rather than initiate the caspase cascade.