Mutations in axonemal dynein assembly factor DNAAF3 cause primary ciliary dyskinesia

Primary ciliary dyskinesia most often arises from loss of the dynein motors that power ciliary beating. Here we show that DNAAF3 (also known as PF22), a previously uncharacterized protein, is essential for the preassembly of dyneins into complexes before their transport into cilia. We identified loss-of-function mutations in the human DNAAF3 gene in individuals from families with situs inversus and defects in the assembly of inner and outer dynein arms. Knockdown of dnaaf3 in zebrafish likewise disrupts dynein arm assembly and ciliary motility, causing primary ciliary dyskinesia phenotypes that include hydrocephalus and laterality malformations. Chlamydomonas reinhardtii PF22 is exclusively cytoplasmic, and a PF22-null mutant cannot assemble any outer and some inner dynein arms. Altered abundance of dynein subunits in mutant cytoplasm suggests that DNAAF3 (PF22) acts at a similar stage as other preassembly proteins, for example, DNAAF2 (also known as PF13 or KTU) and DNAAF1 (also known as ODA7 or LRRC50), in the dynein preassembly pathway. These results support the existence of a conserved, multistep pathway for the cytoplasmic formation of assembly competent ciliary dynein complexes.     

Recombinant scorpine: a multifunctional antimicrobial peptide with activity against different pathogens

Scorpine is an antimicrobial peptide whose structure resembles a hybrid between a defensin and a cecropin. It exhibits antibacterial activity and inhibits the sporogonic development of parasites responsible for murine malaria. In this communication we report the production of scorpine in a heterelogous system, using a specific vector containing its cloned gene. The recombinantly expressed scorpine (RScp) in ^{Anopheles gambie} cells showed antibacterial activity against ^{Bacillus subtilis} and ^{Klebsiella pneumoniae}, at 5 and 10 μM, respectively. It also produced 98% mortality in sexual stages of ^{Plasmodium berghei} at 15 μM and 100% reduction in ^{Plasmodium falciparum} parasitemia at 5 μM. RScp also inhibited virus dengue-2 replication in C6/36 mosquito cells. In addition, we generated viable and fertile transgenic ^Drosophila that overexpresses and correctly secretes RScp into the insect hemolymph, suggesting that the generation of transgenic mosquitoes resistant to different pathogens may be viable. Received 6 May 2008; received after revision 24 July 2008; accepted 29 July 2008     

X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment

Epilepsy and mental retardation limited to females (EFMR) is a disorder with an X-linked mode of inheritance and an unusual expression pattern. Disorders arising from mutations on the X chromosome are typically characterized by affected males and unaffected carrier females. In contrast, EFMR spares transmitting males and affects only carrier females. Aided by systematic resequencing of 737 X chromosome genes, we identified different protocadherin 19 (PCDH19) gene mutations in seven families with EFMR. Five mutations resulted in the introduction of a premature termination codon. Study of two of these demonstrated nonsense-mediated decay of PCDH19 mRNA. The two missense mutations were predicted to affect adhesiveness of PCDH19 through impaired calcium binding. PCDH19 is expressed in developing brains of human and mouse and is the first member of the cadherin superfamily to be directly implicated in epilepsy or mental retardation.     

Four new species of the genus Trichomyia − subgenus Septemtrichomyia Bravo (Diptera: Psychodidae: Trichomyiinae) from Brazil

Septemtrichomyia Bravo is a subgenus of Trichomyia Haliday in Curtis that includes 14 Neotropical species. Here we describe four new species of moth flies from the state of Espírito Santo in Brazil: Trichomyia capixaba sp. nov., T. gabia sp. nov., T. gustavoi sp. nov. and T. menezesi sp. nov. We also provide an updated key to males of the subgenus Septemtrichomyia.

www.zoobank.org/urn:lsid:zoobank.org:pub:4E3C2133-2FCD-4A14-B9A3-A55715931AB4     

Aristotelism of Difference

There is a central doctrine in Aristotle that usually isn’t recognized in its importance: the affirmation of the difference and the plurality. In the course of the centuries, Aristotelism lost which was perhaps its most characteristic and specific feature versus Platonism, that is, its criticism of unity and its defense of plurality. The first principle is not the One but the plurality. The horizon of thinking is not the unity but the diversity of the logos. The unity of the logos presupposes the differences within reality. Heidegger attracted attention to the peculiarity of the practical philosophy of Aristotle. It was the case of dialectics, rhetoric, poetics, ethics, politics, etc. We are referring to knowledges that are art rather than science. Nothing is so differentiated as human action, as it is always performed from a new starting point. Dialectic and rhetorical speeches are always circumscribed to the individual.     

Le “Nonnullae Propositiones de Parabola” di Marino Ghetaldi

Memoria presentata da H. Freudenthal     

Molecular recycling within amyloid fibrils

Amyloid fibrils are thread-like protein aggregates with a core region formed from repetitive arrays of beta-sheets oriented parallel to the fibril axis. Such structures were first recognized in clinical disorders, but more recently have also been linked to a variety of non-pathogenic phenomena ranging from the transfer of genetic information to synaptic changes associated with memory. The observation that many proteins can convert into similar structures in vitro has suggested that this ability is a generic feature of polypeptide chains. Here we have probed the nature of the amyloid structure by monitoring hydrogen/deuterium exchange in fibrils formed from an SH3 domain using a combination of nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry. The results reveal that under the conditions used in this study, exchange is dominated by a mechanism of dissociation and re-association that results in the recycling of molecules within the fibril population. This insight into the dynamic nature of amyloid fibrils, and the ability to determine the parameters that define this behaviour, have important implications for the design of therapeutic strategies directed against amyloid disease.     

Mutations in the gene encoding fibroblast growth factor 10 are associated with aplasia of lacrimal and salivary glands

Autosomal dominant aplasia of lacrimal and salivary glands (ALSG; OMIM 180920 and OMIM 103420) is a rare condition characterized by irritable eyes and dryness of the mouth. We mapped ALSG to 5p13.2-5q13.1, which coincides with the gene fibroblast growth factor 10 (FGF10). In two extended pedigrees, we identified heterozygous mutations in FGF10 in all individuals with ALSG. Fgf10(+/-) mice have a phenotype similar to ALSG, providing a model for this disorder. We suggest that haploinsufficiency for FGF10 during a crucial stage of development results in ALSG.     

Roberts syndrome is caused by mutations in ESCO2, a human homolog of yeast ECO1 that is essential for the establishment of sister chromatid cohesion

Roberts syndrome is an autosomal recessive disorder characterized by craniofacial anomalies, tetraphocomelia and loss of cohesion at heterochromatic regions of centromeres and the Y chromosome. We identified mutations in a new human gene, ESCO2, associated with Roberts syndrome in 15 kindreds. The ESCO2 protein product is a member of a conserved protein family that is required for the establishment of sister chromatid cohesion during S phase and has putative acetyltransferase activity.     

Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity

Multiple organs cooperate to regulate appetite, metabolism, and glucose and fatty acid homeostasis. Here, we identified and characterized lymphatic vasculature dysfunction as a cause of adult-onset obesity. We found that functional inactivation of a single allele of the homeobox gene Prox1 led to adult-onset obesity due to abnormal lymph leakage from mispatterned and ruptured lymphatic vessels. Prox1 heterozygous mice are a new model for adult-onset obesity and lymphatic vascular disease.