Mutations in KANSL1 cause the 17q21.31 microdeletion syndrome phenotype

The chromosome 17q21.31 deletion syndrome is a genomic disorder characterized by highly distinctive facial features, moderate-to-severe intellectual disability, hypotonia and friendly behavior. Here, we show that de novo loss-of-function mutations in KANSL1 (also called KIAA1267) cause a full del(17q21.31) phenotype in two unrelated individuals that lack deletion at 17q21.31. These findings indicate that 17q21.31 deletion syndrome is a monogenic disorder caused by haploinsufficiency of KANSL1.     

In vitro primary immune response resulting from the interaction between bone marrow-derived and thymus cells

Riassunto Globuli rossi di pecora inducono in vitro, in colture miste di cellule spleniche di topi timectomizzati e timociti di topi normali, una risposta immune di tipo emolitico paragonabile a quella di cellule spleniche di topi normali. I dati indicano che la risposta immune delle colture miste risulta dall'interazione dell'antigene con timociti e cellule spleniche di origine midollare.

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Supported by CNEN-Euratom Association Contract. Publication No. 512 of the Euratom Biology Division.     

Early effect of poliomyelitis virus on 5'-nucleotidase activity in HeLa cells]

One of the earlier effects of poliovirus was the maintaining of a high level of Hela cells 5'-nucleotidase activity (maximal efficiency for a virus/cell ratio = 500 ID 50/cell) (ID50:50% Infections Dose). The activity decreased when cells were suspended in the presence of EDTA(EDTA:Ethylene Diamine Tetracetic Acid) and was partially restored by adding 10 mM Mg++ interactions are discussed.     

GTP-dependent twisting of dynamin implicates constriction and tension in membrane fission

Dynamin, a crucial factor in endocytosis, is a member of a family of GTPases that participates in membrane fission. It was initially proposed to act as a machine that constricts and cuts the neck of nascent vesicles in a GTP-hydrolysis-dependent reaction, but subsequent studies suggested alternative models. Here we monitored the effect of nucleotides on dynamin-coated lipid tubules in real time. Addition of GTP, but not of GDP or GTP-gammaS, resulted in twisting of the tubules and supercoiling, suggesting a rotatory movement of the helix turns relative to each other during GTP hydrolysis. Rotation was confirmed by the movement of beads attached to the tubules. Twisting activity produced a longitudinal tension that was released by tubule breakage when both ends of the tubule were anchored. Fission also occurred when dynamin and GTP were added to lipid tubules that had been generated from liposomes by the motor activity of kinesin on microtubules. No fission events were observed in the absence of longitudinal tension. These findings demonstrate a mechanoenzyme activity of dynamin in endocytosis, but also imply that constriction is not sufficient for fission. At the short necks of endocytic vesicles, other factors leading to tension may cooperate with the constricting activity of dynamin to induce fission.     

Correspondence Analysis with Linear Constraints of Ordinal Cross-Classifications

Within the non-iterative procedures for performing a correspondence analysis with linear constraints, a strategy is proposed to impose linear constraints in analyzing a contingency table with one or two ordered sets of categories. At the heart of the approach is the partition of the Pearson chi-squared statistics which involves terms that summarize the association between the nominal/ordinal variables using bivariate moments based on orthogonal polynomials. Linear constraints are then included directly in suitable matrices reflecting the most important components, overcoming also the problem of imposing linear constraints based on subjective decisions.     

Essay review

This paper treats van Helmont's attack on Aristotle as an example of the difficulty of accounting for one author's attack on another by simply comparing the texts of the two authors. The Aristotle that van Helmont is attacking is the Aristotle represented in contemporary textbooks, and the attack on his authority is closely connected to the attack on the importance of verbal disputation in education. The importance of knowledge of Aristotle and of argumentative skills means van Helmont displays them to claim competence in them, while arguing they are worthless, and states many of his own doctrines as denials of Aristotelian doctrines. After a brief account of van Helmont's cosmology, three texts of his are examined: the conclusion of Causae et initia naturalium, where van Helmont demonstrates the worthlessness of Aristotelian method, by giving an example of his own method's greater success, the beginning of Physica Aristotelis et Galeni ignara, where he argues in Aristotelian terms against an Aristotelian definition of nature, and his general attack on Aristotelian method and on verbal disputation in Logica inutilis.     

Phosphoinositides in cell regulation and membrane dynamics

Inositol phospholipids have long been known to have an important regulatory role in cell physiology. The repertoire of cellular processes known to be directly or indirectly controlled by this class of lipids has now dramatically expanded. Through interactions mediated by their headgroups, which can be reversibly phosphorylated to generate seven species, phosphoinositides play a fundamental part in controlling membrane-cytosol interfaces. These lipids mediate acute responses, but also act as constitutive signals that help define organelle identity. Their functions, besides classical signal transduction at the cell surface, include regulation of membrane traffic, the cytoskeleton, nuclear events and the permeability and transport functions of membranes.     

Recruitment and regulation of phosphatidylinositol phosphate kinase type 1 gamma by the FERM domain of talin

Membrane phosphoinositides control a variety of cellular processes through the recruitment and/or regulation of cytosolic proteins. One mechanism ensuring spatial specificity in phosphoinositide signalling is the targeting of enzymes that mediate their metabolism to specific subcellular sites. Phosphatidylinositol phosphate kinase type 1 gamma (PtdInsPKI gamma) is a phosphatidylinositol-4-phosphate 5-kinase that is expressed at high levels in brain, and is concentrated at synapses. Here we show that the predominant brain splice variant of PtdInsPKI gamma (PtdInsPKI gamma-90) binds, by means of a short carboxy-terminal peptide, to the FERM domain of talin, and is strongly activated by this interaction. Talin, a principal component of focal adhesion plaques, is also present at synapses. PtdInsPKI gamma-90 is expressed in non-neuronal cells, albeit at much lower levels than in neurons, and is concentrated at focal adhesion plaques, where phosphatidylinositol-4,5-bisphosphate has an important regulatory role. Overexpression of PtdInsPKI gamma-90, or expression of its C-terminal domain, disrupts focal adhesion plaques, probably by local disruption of normal phosphoinositide balance. These findings define an interaction that has a regulatory role in cell adhesion and suggest new similarities between molecular interactions underlying synaptic junctions and general mechanisms of cell adhesion.