Mutant deoxynucleotide carrier is associated with congenital microcephaly

The disorder Amish microcephaly (MCPHA) is characterized by severe congenital microcephaly, elevated levels of alpha-ketoglutarate in the urine and premature death. The disorder is inherited in an autosomal recessive pattern and has been observed only in Old Order Amish families whose ancestors lived in Lancaster County, Pennsylvania. Here we show, by using a genealogy database and automated pedigree software, that 23 nuclear families affected with MCPHA are connected to a single ancestral couple. Through a whole-genome scan, fine mapping and haplotype analysis, we localized the gene affected in MCPHA to a region of 3 cM, or 2 Mb, on chromosome 17q25. We constructed a map of contiguous genomic clones spanning this region. One of the genes in this region, SLC25A19, which encodes a nuclear mitochondrial deoxynucleotide carrier (DNC), contains a substitution that segregates with the disease in affected individuals and alters an amino acid that is highly conserved in similar proteins. Functional analysis shows that the mutant DNC protein lacks the normal transport activity, implying that failed deoxynucleotide transport across the inner mitochondrial membrane causes MCPHA. Our data indicate that mitochondrial deoxynucleotide transport may be essential for prenatal brain growth.     

Two types of viruslike particles inDrosophila midgut

Résumé On a trouvé des particules hexagonales, comme des virus, de deux grandeurs, dans les cellules de la partie centrale de l'intestin de laDrosophile. Les particules les plus grosses étaient dans le cytoplasme et les plus petites dans le noyau. L'apparence de la distribution de ces particules sont en fonction de l'âge de la mouche.

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Part of this work was supported by research grant No. AM 12818 of the National Institute of Arthritis and Metabolic Diseases.     

Two functionally distinct calcium pools in the excitation-contraction coupling process

Zusammenfassung Es wird angenommen, dass mindestens zwei Fraktionen von intrazellulärem Kalzium am Kupplungsprozess zwischen Reizung und Kontraktion des Herzens beteiligt sind.

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This work was supported by grants from the Manitoba Heart Foundation and the Medical Research Council of Canada. We thank Mr.Stan Vivian for development of the PDP8/I computer program to analyze the calcium uptake curves.     

The physiological effects of ionic lanthanum on the insect blood-brain barrier

Summary Lanthanum had a small effect on the barrier, but did not significantly increase its sodium or patossium permeability. There was no effect on nerve conduction unless the barrier was deliberately damaged. The results lend confidence to the use of lanthanum as an extracellular tracer.     

Uptake of exogenous protein by supraependymal cells of the feline area postrema.

Supraependymal cells occurring on the surface of the feline area postrema were examined for phagocytic ability. It was shown that they could ingest exogenous horseradish peroxidase that was experimentally introduced into the brain ventricular system. The cells thus bear functional as well as ultrastructural attributes of macrophages, similar to those found in the third ventricle and subarachnoid space.     

Pt/陶瓷电极上醇类的阳极氧化作用及其钼和钨的添加对电极活性的影响

采用电沉积Pt在陶瓷膜的方法制得了一种新型的可用于醇类阳极氧化的陶瓷基底电极,采用在电沉积前用氧化钨的溶胶或硅钨酸或硅钼酸的溶液浸渍陶瓷膜的方法可将钨和钼添加到电极中.实验发现钨和钼的添加可以十分显著地提高催化剂的活性,如对于甲醇的阳极氧化,添加硅钼酸的电极上的电流密度可达到187 mA/cm2,为相同条件下不含硅钼酸的电极的5倍多.对于乙醇的阳极氧化也得到了相同的结果.     

Accurate whole human genome sequencing using reversible terminator chemistry

DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high-quality sequence. We demonstrate application of this approach to human genome sequencing on flow-sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from >30x average depth of paired 35-base reads. We characterize four million single-nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications.