Mitochondrial non-syndromic sensorineural hearing loss: a clinical, audiological and pathological study from Italy, and revision of the literature

Over the last decade, a number of distinct mutations in the mtDNA (mitochondrial DNA) have been found to be associated with both syndromic and non-syndromic forms of hearing impairment. Their real incidence as a cause of deafness is poorly understood and generally underestimated. Among the known mtDNA mutations, the A1555G mutation in the 12S gene has been identified to be one of the most common genetic cause of deafness, and it has been described to be both associated to non-syndromic progressive SNHL (sensorineural hearing loss) and to aminoglycoside-induced SNHL. In the present study, we have investigated the presence of mtDNA alterations in patients affected by idiopathic non-syndromic SNHL, both familiar and sporadic, in order to evaluate the frequency of mtDNA alterations as a cause of deafness and to describe the audiological manifestations of mitochondrial non-syndromic SNHL. In agreement with previous studies, we found the A1555G mutation to be responsible for a relevant percentage (5.4%) of cases affected with isolated idiopathic sensorineural hearing impairment.     

The behaviour of deoxyhexose trihaloacetimidates in selected glycosylations

Armed deoxyhexose glycosyl donors are very reactive and sometimes too uncontrollably activated in glycosylation reactions; yields can be thereby reduced, especially when unreactive glycosyl acceptors are involved. In this paper, the behaviour of a range of deoxyhexose trihaloacetimidate (trichloro- and N-phenyl trifluoro-) donors is compared in some selected glycosylations towards biologically relevant targets. The selected N-phenyl trifluoroacetimidates often afforded best results in terms of both donor synthesis and glycosylation yield.     

The Matricellular Protein Periostin Is Required for Sost Inhibition and the Anabolic Response to Mechanical Loading and Physical Activity

Periostin (gene Postn) is a secreted extracellular matrix protein involved in cell recruitment and adhesion and plays an important role in odontogenesis. In bone, periostin is preferentially expressed in the periosteum, but its functional significance remains unclear. We investigated Postn^−/− mice and their wild type littermates to elucidate the role of periostin in the skeletal response to moderate physical activity and direct axial compression of the tibia. Furthermore, we administered a sclerostin-blocking antibody to these mice in order to demonstrate the influence of sustained Sost expression in their altered bone phenotypes. Cancellous and cortical bone microarchitecture as well as bending strength were altered in Postn^−/− compared with Postn^+/+ mice. Exercise and axial compression both significantly increased bone mineral density and trabecular and cortical microarchitecture as well as biomechanical properties of the long bones in Postn^+/+ mice by increasing the bone formation activity, particularly at the periosteum. These changes correlated with an increase of periostin expression and a consecutive decrease of Sost in the stimulated bones. In contrast, mechanical stimuli had no effect on the skeletal properties of Postn^−/− mice, where base-line expression of Sost levels were higher than Postn^+/+ and remained unchanged following axial compression. In turn, the concomitant injection of sclerostin-blocking antibody rescued the bone biomechanical response in Postn^−/− mice. Taken together, these results indicate that the matricellular periostin protein is required for Sost inhibition and thereby plays an important role in the determination of bone mass and microstructural in response to loading.     

Function-dependent development in a colonial animal

How does the way an organism functions affect its subsequent development? Bryozoans are colonial animals that capture suspended food particles from water currents they generate using crowns of ciliated tentacles (lophophores). In many encrusting bryozoans the water passes through and then under the lophophores until it exits the colony at "chimneys" where the lophophores spread apart to form an opening. To determine whether these water currents can induce the formation of new chimneys, I augmented the excurrent flow by injecting seawater into the colony. New chimneys began to develop near the site of seawater injection within as little as one to two days. New chimneys rarely began to develop within this time interval at control sites where I did not inject seawater. This shows that fluid flow controls development in an external fluid transport system lacking pipe-like conduits, as has been found in the vertebrate circulatory system, an internal fluid transport system with pipe-like conduits. These fluid transport systems show feedback between the way they function and their own development. This kind of "function-dependent development" should be differentiated from phenotypic plasticity, since the developing system, not the environment, produces the signals that induce morphological change.     

Climate determinants of breeding and wintering ranges of lesser kestrels in Italy and predicted impacts of climate change

Climate warming would theoretically create conditions for the breeding range expansion of pseudo‐steppe Mediterranean and long‐distance migrant species and provide the possibility for these to overwinter in the same breeding areas. However, contemporary changes in rainfall regimes might have negative effects on the climate suitability and in turn, shrink species potential range. The lesser kestrel Falco naumanni is highly sensitive to rainfall oscillations and has recently extended its Italian breeding range towards northern latitudes and increasing its wintering records. We modelled the effects of temperature and rainfall on current and future climate suitability for lesser kestrels in both the breeding and wintering periods by using MaxEnt. Models were based on the distribution of 298 colonies and 40 wintering records. Future climate suitability was assessed under eight different scenarios. Spring rainfall amount resulted as the main determinant of breeding climate suitability, so its predicted reduction will determine a shrinkage in suitable areas (–42.10% in 2050; –32.07% in 2070). Specifically, the 66.05% of Italian colonies will be outside the climatically suitable area by 2050. However wide areas, suitable under current climate conditions, are still not occupied by lesser kestrel and allow the potential expansion of its Italian breeding range in the short term. Temperature seasonality mainly determined the species’ winter climate suitability, which is overall predicted to boost in the next decades (+145.03% in 2050; and +123.91% in 2070). All but one future scenarios predicted a northward shift of about 40 km for both breeding and wintering climate suitability. Despite its recent expansion, we have found that climate change will pose conservation concerns for the Italian breeding population of lesser kestrels. Indeed, changes in non‐climate factors will also outline the future suitability of the Italian range for lesser kestrels in both seasons with effects that might both strengthen or mitigate climate effects.     

Mitochondrial Ca2+ homeostasis in health and disease

Although it has long been known that mitochondria possess a complex molecular repertoire for accumulating and releasing Ca2+, only in recent years has a large body of data demonstrated that these organelles promptly respond to Ca(2+)-mediated cell stimulations. In this contribution, we will review the principles of mitochondrial Ca2+ homeostasis and its signaling role in different physiological and pathological conditions.     

Role of two dileucine-like motifs in insulin receptor anchoring to microvilli

In the absence of ligand, the insulin receptor is maintained on microvilli on the cell surface. A dileucine motif (LL(986-987)) is necessary but not sufficient for this anchoring, which also required the presence of additional sequence(s) downstream of position 1000. The aim of the present study was to identify this (these) additional sequence(s). First, exons 16 or 17 were fused to the extracellular and transmembrane domains of complement receptor 1 and stably expressed in Chinese hamster ovary cells. Results obtained indicate that exon 17 is sufficient for anchoring to microvilli. Second, analysis of insulin receptor mutants truncated within exon 17 demonstrated that whereas receptors truncated at position 1000 showed no preferential association with microvilli, receptors truncated at position 1012 displayed a level of association identical to that of the full-length insulin receptor. Third, mutation of a diisoleucine motif (II(1006-1007)) present within this 12-amino acid stretch abrogated the preferential association of the receptor with microvilli. These results indicate that the domain required for association of insulin receptor with microvilli is contained within the region encoded by exon 17 and that, within this sequence, two dileucine-like motifs (LL(986-987) and II(1006-1007)) play a crucial role.     

Secretion of alpha-amylase from Pseudoalteromonas haloplanktis TAB23: two different pathways in different hosts

Secretion of cold-adapted alpha-amylase from Pseudoalteromonas haloplanktis TAB23 was studied in three Antarctic bacteria. We demonstrated that the enzyme is specifically secreted in the psychrophilic hosts even in the absence of a protein domain that has been previously reported to be necessary for alpha-amylase secretion in Escherichia coli. The occurrence of two different secretion pathways in different hosts is proposed.