Studies on the quaternary structure of the first enzyme for histidine biosynthesis

Resumen Se han realizado estudios de asociación-disociación por filtración en gel con el primer enzima de la biosíntesis de histidina enEscherichia coli, en presencia de sustratos y ligandos. Se observa una interconversión reversible entre las formas dímero, tetrámero y exámero, y una agregación irreversible de orden superior.     

Calcium ion binding to blood cell surfaces

Zusammenfassung Neue Erkenntnisse über die quantitativen Zusammenhänge von fixierten, negativen Ladungen an Zellmembranen und ihren Interaktionen mit Kalzium-Ionen. Die elektrophoretische Analyse der Bindung von Ca-Ionen an menschliche polymorphkernige Leukozyten und rote Blutkörperchen deutet die Anwesenheit von mindestens 3 verschiedenen anionischen Ladungskonfigurationen in der peripheren Zone der Zellen an. Die zwischen den Ca-Ionen und den Oberflächen-Anionen existierenden elektrochemischen freien Bindungsenergien sind relativ schwach; daraus folgert, dass die Ca-Ionen nur schlechte Komponenten für eine direkte interzelluläre überbrückung darstellen.     

Transmission of cutaneous leishmaniasis by sand flies is enhanced by regurgitation of fPPG

Sand flies are the exclusive vectors of the protozoan parasite Leishmania, but the mechanism of transmission by fly bite has not been determined nor incorporated into experimental models of infection. In sand flies with mature Leishmania infections the anterior midgut is blocked by a gel of parasite origin, the promastigote secretory gel. Here we analyse the inocula from Leishmania mexicana-infected Lutzomyia longipalpis sand flies. Analysis revealed the size of the infectious dose, the underlying mechanism of parasite delivery by regurgitation, and the novel contribution made to infection by filamentous proteophosphoglycan (fPPG), a component of promastigote secretory gel found to accompany the parasites during transmission. Collectively these results have important implications for understanding the relationship between the parasite and its vector, the pathology of cutaneous leishmaniasis in humans and also the development of effective vaccines and drugs. These findings emphasize that to fully understand transmission of vector-borne diseases the interaction between the parasite, its vector and the mammalian host must be considered together.     

Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome

Joubert syndrome is a congenital brain malformation of the cerebellar vermis and brainstem with abnormalities of axonal decussation (crossing in the brain) affecting the corticospinal tract and superior cerebellar peduncles. Individuals with Joubert syndrome have motor and behavioral abnormalities, including an inability to walk due to severe clumsiness and 'mirror' movements, and cognitive and behavioral disturbances. Here we identified a locus associated with Joubert syndrome, JBTS3, on chromosome 6q23.2-q23.3 and found three deleterious mutations in AHI1, the first gene to be associated with Joubert syndrome. AHI1 is most highly expressed in brain, particularly in neurons that give rise to the crossing axons of the corticospinal tract and superior cerebellar peduncles. Comparative genetic analysis of AHI1 indicates that it has undergone positive evolutionary selection along the human lineage. Therefore, changes in AHI1 may have been important in the evolution of human-specific motor behaviors.