Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL

Autosomal recessive osteopetrosis is usually associated with normal or elevated numbers of nonfunctional osteoclasts. Here we report mutations in the gene encoding RANKL (receptor activator of nuclear factor-KB ligand) in six individuals with autosomal recessive osteopetrosis whose bone biopsy specimens lacked osteoclasts. These individuals did not show any obvious defects in immunological parameters and could not be cured by hematopoietic stem cell transplantation; however, exogenous RANKL induced formation of functional osteoclasts from their monocytes, suggesting that they could, theoretically, benefit from exogenous RANKL administration.     

The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease.

We identified three distinct mutations and six mutant alleles in GDAP1 in three families with axonal Charcot-Marie-Tooth (CMT) neuropathy and vocal cord paresis, which were previously linked to the CMT4A locus on chromosome 8q21.1. These results establish the molecular etiology of CMT4A (MIM 214400) and suggest that it may be associated with both axonal and demyelinating phenotypes.     

Polyacetylenes from the spongePetrosia ficiformis found in dark caves

Summary Several high molecular weight polyacetylenes have been isolated from the spongePetrosia ficiformis found in dark caves. These compounds are related to, but different from, the polyacetylenes isolated from the same sponge living in its usual habitat.This work is a part of the Progetto finalizzato per l'Oceanografia e i Fondi Marini, CNR, Roma.The authors thank Mr G. Scognamiglio for the HPLC work, Mr C. Di Pinto for the NMR spectra and Mr G. Villani for the collection of the sponge.     

Arboreality predicts Batrachochytrium dendrobatidis infection level in tropical direct-developing frogs

Pathogen-mediated changes in host behaviour can result from hosts altering their habitat preferences. Although infection risk with pathogenic fungus Batrachochytrium dendrobatidis in amphibians is associated with environments favouring its growth, the relationship with microhabitat use has not been examined. Here, we aim to determine if microhabitats used by frogs during their nocturnal activity predict B. dendrobatidis prevalence and infection intensity. Our focal host, Eleutherodactylus coqui, is a habitat generalist that uses multiple habitats from the forest floor to the canopy. We analysed data on B. dendrobatidis occurrence in 157 adults and 122 juveniles at El Yunque National forest in Puerto Rico. We categorized each individual’s nocturnal microhabitat as forest floor, curled palm fronds in the floor, arboreal bromeliads and foliage or tree trunks 50 cm to 2.5 m above ground. We found that frogs on the forest floor had the greatest B. dendrobatidis prevalence (73%), compared with those active in vegetation above ground (55%). Overall, the probability of B. dendrobatidis infection in frogs using microhabitats on the forest floor was twice as great as for those on arboreal substrates. Differences in B. dendrobatidis prevalence and intensity in E. coqui may be explained by specific abiotic conditions of microenvironments (temperature and humidity) affecting both pathogen and host, and by the age-specific ecological requirements of hosts. Adults were found to be most active in microhabitats where individuals had lower infection burdens, suggesting pathogen-modulated habitat choice. This work has important implications for the evolutionary dynamics of enzootic diseases and provides data that may inform potential mitigation strategies against a generalist amphibian pathogen.     

Melatonin transport into mitochondria

Melatonin is a well-known, nighttime-produced indole found in bacteria, eukaryotic unicellulars, animals or vascular plants. In vertebrates, melatonin is the major product of the pineal gland, which accounts for its increase in serum during the dark phase, but it is also produced by many other organs and cell types. Such a wide distribution is consistent with its multiple and well-described functions which include from the circadian regulation and adaptation to seasonal variations to immunomodulatory and oncostatic actions in different types of tumors. The discovery of its antioxidant properties in the early 1990s opened a new field of potential protective functions in multiple tissues. A special mention should be made regarding the nervous system, where the indole is considered a major neuroprotector. Furthermore, mitochondria appear as one of the most important targets for the indole’s protective actions. Melatonin’s mechanisms of action vary from the direct molecular interaction with free radicals (free radical scavenger) to the binding to membrane (MLT1A and MLT1B) or nuclear receptors (RZR/RORα). Receptor binding has been associated with some, but not all of the indole functions reported to date. Recently, two new mechanisms of cellular uptake involving the facilitative glucose transporters GLUT/SLC2A and the proton-driven oligopeptide transporter PEPT1/2 have been reported. Here we discuss the potential importance that these newly discovered transport systems could have in determining the actions of melatonin, particularly in the mitochondria. We also argue the relative importance of passive diffusion vs active transport in different parts of the cell.     

Nest architecture in polydomous grass-cutting ants (Acromyrmex balzani)

Acromyrmex balzani is a grass-cutting ant species frequently found in Cerrado areas. However, little is known about the architecture of the polydomous nests of this ant. Fifteen A. balzani nests located in a cerrado region in Botucatu, São Paulo, Brazil, were studied. The polydomous nests were studied in three ways. First, we investigated the architecture in nests moulded with cement and without moulding. Second, we performed an aggressiveness test among workers in different subnests and nests. Third, we excavated the nest and collected the colony to measure the population, verifying the existence or not of a queen in all nests. A cement mould was made of seven nests to permit better visualization of internal structures such as chambers and tunnels. Eight nests were excavated without moulding and white neutral talc was used to highlight the parts of the nests. After excavation, the depth and dimensions (length, width and height) of the chambers were measured. The results showed that the nests had a single entrance hole whose structure consisted of straw and other plant residues in winter. Mounds of loose soil, if present, were found 6–48 cm from the hole. The number of chambers containing fungus ranged from one to five, with the first being found a few centimetres beneath the ground surface (4 cm) and the last up to a maximum depth of 160 cm. The length of the tunnels ranged from 12 to 28 cm. These tunnels were built in a vertical or inclined position, leading to the chambers. No waste chambers were found, with the waste being deposited externally. Additionally, the polydomous nests contained one to eight subnests. In the aggressiveness test, when concolonial workers were confronted, no aggressiveness was observed. In contrast, when allocolonial workers were confronted, there was a high incidence of aggression among them. Excavation of polydomous nests showed only one queen for each polydomous nest, i.e. subnests with a single queen. Our study contributes to a better understanding of the so far unknown nest architecture of the polydomous grass-cutting ant A. balzani.     

Activation of stress signalling pathways enhances tolerance of fungi to chemical fungicides and antifungal proteins

Fungal disease is an increasing problem in both agriculture and human health. Treatment of human fungal disease involves the use of chemical fungicides, which generally target the integrity of the fungal plasma membrane or cell wall. Chemical fungicides used for the treatment of plant disease, have more diverse mechanisms of action including inhibition of sterol biosynthesis, microtubule assembly and the mitochondrial respiratory chain. However, these treatments have limitations, including toxicity and the emergence of resistance. This has led to increased interest in the use of antimicrobial peptides for the treatment of fungal disease in both plants and humans. Antimicrobial peptides are a diverse group of molecules with differing mechanisms of action, many of which remain poorly understood. Furthermore, it is becoming increasingly apparent that stress response pathways are involved in the tolerance of fungi to both chemical fungicides and antimicrobial peptides. These signalling pathways such as the cell wall integrity and high-osmolarity glycerol pathway are triggered by stimuli, such as cell wall instability, changes in osmolarity and production of reactive oxygen species. Here we review stress signalling induced by treatment of fungi with chemical fungicides and antifungal peptides. Study of these pathways gives insight into how these molecules exert their antifungal effect and also into the mechanisms used by fungi to tolerate sub-lethal treatment by these molecules. Inactivation of stress response pathways represents a potential method of increasing the efficacy of antifungal molecules.