Modeling the Role of Negative Cooperativity in Metabolic Regulation and Homeostasis

A significant proportion of enzymes display cooperativity in binding ligand molecules, and such effects have an important impact on metabolic regulation. This is easiest to understand in the case of positive cooperativity. Sharp responses to changes in metabolite concentrations can allow organisms to better respond to environmental changes and maintain metabolic homeostasis. However, despite the fact that negative cooperativity is almost as common as positive, it has been harder to imagine what advantages it provides. Here we use computational models to explore the utility of negative cooperativity in one particular context: that of an inhibitor binding to an enzyme. We identify several factors which may contribute, and show that acting together they can make negative cooperativity advantageous.     

Cytogenetic characteristics of a population of Chironomus riparius Meigen 1804 (Diptera, Chironomidae) from a polluted Po river station

A population of Chironomus riparius from a Po river station near Moncalieri (a trace-metal polluted station) was studied. In this population was established a great variability of band structure of polytene chromosomes as well as paracentric heterozygous inversions, deletions, deficiencies, partial breaks, diploid chromosome fragments, and changes in functional activity and appearance of heterochromatin. In arms A through F, some bands had an increased size compared to the standard chromosomic map. Some bands appeared in a heterozygous or normal homozygous state or were amplified. In all arms, many condensed stable bands appeared in the decondensed state when compared to the standard map. Asynaptic zones in arms E and G as well as heterozygous Balbiani rings and NORs were established. Very often the 4th chromosome was almost completely heteropycnotic and looded like a pompon chromosome. For the first time in this species, a high frequency of ectopic pairings of different arms was observed. Telomeric regions involved in ectopic pairings had a granular appearance, as did some centromeres. The hypothesis is advanced that such a high frequency of structural rearrangements could be correlated with genomic distribution of specific mobile elements.     

Release of radiolabeled dopamine,p-tyramine,andm-tyramine from rat striatal slices by some aminotetralins

The effect of several 2-aminotetralins (2ATs) on the uptake and release of [¹⁴C] dopamine and [³H]m- or [³H]p-tyramine by rat striatal slices was examined. 6,7-Dihydroxy-2AT (6,7OHAT) and 5,6-dihydroxy-2-methyl-AT (5,6OHMeAT) were the most potent uptake inhibitors as well as the most potent releasers of the three labeled amines. The 5-, 6-, and 7-hydroxy-2-N,N-dipropyl-ATs (5-, 6-, and 7OHdiPrAT) and 5,6-dihydroxy-2-N,N-dipropyl-AT (5,6OHdiPrAT) significantly inhibited the uptakes of the three labeled amines, but they released only the tyramines. The dipropyl substitution of a 2AT appeared to confer a tyraminergic specificity to its release properties. To verify this supposition, 2AT was compared to 2-N,N-dipropyl-AT (diPrAT). Although 2AT released both [³H]p-tyramine and [¹⁴C]dopamine, diPrAT released only [³H]p-tyramine. None of the compounds, however, differentiated betweenm- andp-tyramine. It was concluded that the release of tyramines could be implicated in the actions of some of the 2ATs and that the tyramines can be transported independently from dopamine.     

Erythropoiesis in cultures of dispersed cell preparations from early chick blastodiscs

Optimal conditions were determined for differentiation of erythroid cells in liquid cultures of dispersed cell preparations from chick blastodiscs at the primitive streak and head-fold stages of development. Most of the unattached erythroid cells free in the medium were mature erythrocytes.     

Candidiasis: Predisposing Factors,Prevention, Diagnosis and Alternative Treatment

Candidiasis is the most common opportunistic yeast infection. Candida species and other microorganisms are involved in this complicated fungal infection, but Candida albicans continues to be the most prevalent. In the past two decades, it has been observed an abnormal overgrowth in the gastrointestinal, urinary and respiratory tracts, not only in immunocompromised patients, but also related to nosocomial infections and even in healthy individuals. There is a widely variety of causal factors that contribute to yeast infection which means that candidiasis is a good example of a multifactorial syndrome. Due to rapid increase in the incidence in these infections, this is the subject of numerous studies. Recently, the focus of attention is the treatment and, above all, the prevention of those complications. The diagnosis of candidiasis could become quite complicated. Prevention is the most effective “treatment,” much more than eradication of the yeast with antifungal agents. There are several aspects to consider in the daily routine that can provide a strength protection. However, a therapeutic approach is necessary when the infection is established, and therefore, other alternatives should be explored. This review provides an overview on predisposition factors, prevention and diagnosis of candidiasis, highlighting alternative approaches for candidiasis treatment.     

Binding and transport of SFPQ-RNA granules by KIF5A/KLC1 motors promotes axon survival

Complex neural circuitry requires stable connections formed by lengthy axons. To maintain these functional circuits, fast transport delivers RNAs to distal axons where they undergo local translation. However, the mechanism that enables long-distance transport of RNA granules is not yet understood. Here, we demonstrate that a complex containing RNA and the RNA-binding protein (RBP) SFPQ interacts selectively with a tetrameric kinesin containing the adaptor KLC1 and the motor KIF5A. We show that the binding of SFPQ to the KIF5A/KLC1 motor complex is required for axon survival and is impacted by KIF5A mutations that cause Charcot-Marie Tooth (CMT) disease. Moreover, therapeutic approaches that bypass the need for local translation of SFPQ-bound proteins prevent axon degeneration in CMT models. Collectively, these observations indicate that KIF5A-mediated SFPQ-RNA granule transport may be a key function disrupted in KIF5A-linked neurologic diseases and that replacing axonally translated proteins serves as a therapeutic approach to axonal degenerative disorders.