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.     

Reproductive cycle of the Belding ground squirrel ( Spermophilus beldingi beldingi ): seasonal and age differences

The reproductive cycle in Belding ground squirrels was studied in the Sierra Nevada Mountains at two locations, one at 2,100 m elevation, the other at 3,000 m. Adults emerged from hibernation completely prepared physiologically for reproduction. Males tended to emerge slightly ahead of females and yearlings tended to emerge later than adults. Yearling females were fertile but produced smaller litters than adults, 4.48 vs. 6.31. Yearling males were infertile. They exhibited a slight seasonal cycle in testicular growth but did not reach sexual maturity. Testicular growth and spermatogenesis were incipient in many adults and in yearlings prior to hibernation.       

Interaction of lipid transfer protein with plasma lipoproteins and cell membranes

Summary The hydrophobic lipid components of lipoproteins, cholesteryl ester and triglyceride, are transferred between all lipoproteins by a specific plasma glycoprotein, termed lipid transfer protein (LTP). LTP facilitates lipid transfer by an exchange process in which cholesteryl ester and triglyceride compete for transfer. Thus, LTP promotes remodeling of the lipoprotein structure, and plays an important role in the intravascular metabolism of these particles and in the lipoprotein-dependent pathways of cholesterol clearance from cells. The properties of LTP, its mechanisms of action, its roles in lipoprotein metabolism, and its modes of regulation are reviewed along with recent data that suggest a possible role for this protein in directly modifying cellular lipid composition.     

Potentiation of the immunosuppressive effects of cytoxan by hyperbaric oxygen

Zusammenfassung Die intermittierende Anwendung hyperbarischen Sauerstoffs erhöht die die Antikörper unterdrückende Wirkung von Cytoxan bei Mäusen, die vorher mit Ochsenserum-Albumin und Freunds Adjuvans immunisiert worden waren. Der Wirkungsmechanismus des Sauerstoffs wird als Verhinderung der Transformation von kleinen Lymphocyten in immunbiologisch aktive Stammzellen gedeutet.

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Supported by U.S. Atomic Energy Commission Contract No. RLO-1927-13.