Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations

Evidence for the etiology of autism spectrum disorders (ASDs) has consistently pointed to a strong genetic component complicated by substantial locus heterogeneity. We sequenced the exomes of 20 individuals with sporadic ASD (cases) and their parents, reasoning that these families would be enriched for de novo mutations of major effect. We identified 21 de novo mutations, 11 of which were protein altering. Protein-altering mutations were significantly enriched for changes at highly conserved residues. We identified potentially causative de novo events in 4 out of 20 probands, particularly among more severely affected individuals, in FOXP1, GRIN2B, SCN1A and LAMC3. In the FOXP1 mutation carrier, we also observed a rare inherited CNTNAP2 missense variant, and we provide functional support for a multi-hit model for disease risk. Our results show that trio-based exome sequencing is a powerful approach for identifying new candidate genes for ASDs and suggest that de novo mutations may contribute substantially to the genetic etiology of ASDs.     

Pharmacological study of para-aminoclonidine, an alpha sympathomimetic]

Para-aminoclonidine is a more potent alpha-adrenergic agent than clonidine; in vitro on Rat aorta it is 150 times more active than NE, in vivo on pithed Rat it is still twice as active. The hypotensive action of paraaminoclondine is only manifested when given intraventricularly. In the conscious Rat, it has a diuretic action when given per os. Following IV injection in the anaesthetized Dog, the para-aminoclonidine induces an essentially hydric diuresis which is independet of its hypertensive action.     

The absence of normal serum proteins in lymphoma patients revealed by disc electrophoresis

Résumé La méthode d'électrophorèse en gel avec coloration spéciale est utilisée ici pour la comparaison des protéines sériques de 97 malades porteurs de néoplasme avec celles de 33 contrÔles normaux. Deux bandes, présentes dans tous les contrÔles représentant aux moins deux différentes protéines avec une mobilité d'-2-globuline, sont absentes dans 60 sérums de malades.     

Three unpublished letters to Charles Darwin: the solution to a ‘geometrico-geological’ problem

While Charles Darwin wrote his Observations on South America, he often sought the advice and help of other scientists in solving specific problems. Three letters that the Cambridge geologist and mathematician William Hopkins wrote to Darwin exemplify such aid. In these letters Hopkins was able to show Darwin how he could calculate the position of the sedimentary beds on the Chonos Archipelago, which Darwin had visited. In his first letter Hopkins sent a solution, part of which eluded Darwin. Darwin's letters to Hopkins have not yet been found, but two additional letters gave Darwin the solution he was looking for.     

Comparative metabolic studies with Natulan®, methylhydrazine and methylamine in rats

Zusammenfassung Nach intraperitonealer Verabreichung von Natulan^®, Methylamin oder Methylhydrazin an Ratten konnte im Urin neben den verabreichten Stoffen Methylamin nachgewiesen werden, dagegen wurde Methylhydrazin als Metabolit von Natulan^® nicht gefunden. Das Auftreten von Methylamin nach Gabe der erwähnten Hydrazinverbindungen zeigt, dass der Ratten-organismus nicht nur, wie bisher bekannt, aromatische Azoverbindungen an der N-N-Bindung spalten kann, sondern auch aliphatisch-araliphatische.

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Registered trade mark forp-(isopropylcarbamoyl)benzyl methylhydrazine, a cytostatic methylhydrazine derivative.     

Reflex activity of single preganglionic sympathetic fibres during coronary occlusion

Résumé La décharge de fibres sympathiques préganglionnaires isolées, faisant probablement partie de l'innervation efférente du cur, a été étudiée sur des chats, soit anésthésiés, soit décérébrés, soit spinalisés, par rapport à l'occlusion d'un segment de l'artère coronaire de gauche.

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This work was supported in part by Consiglio Nazionale delle Ricerche, Group of Experimental Medicine. The authors wish to express their gratitude to Dr. E. R.Perl for kindly showing them his dissecting techniques.