Ligand-specific recycling profiles determine distinct potential for chronic analgesic tolerance of delta-opioid receptor (DOPr) agonists

δ-opioid receptor (DOPr) agonists have analgesic efficacy in chronic pain models but development of tolerance limits their use for long-term pain management. Although agonist potential for inducing acute analgesic tolerance has been associated with distinct patterns of DOPr internalization, the association between trafficking and chronic tolerance remains ill-defined. In a rat model of streptozotocin (STZ)-induced diabetic neuropathy, deltorphin II and TIPP produced sustained analgesia  following daily (intrathecal) i.t. injections over six days, whereas similar treatment with SNC-80 or SB235863 led to progressive tolerance and loss of the analgesic response. Trafficking assays in murine neuron cultures showed no association between the magnitude of ligand-induced sequestration and development of chronic tolerance. Instead, ligands that supported DOPr recycling were also the ones producing sustained analgesia over 6-day treatment. Moreover, endosomal endothelin-converting enzyme 2 (ECE2) blocker 663444 prevented DOPr recycling by deltorphin II and TIPP and precipitated tolerance by these ligands. In conclusion, agonists, which support DOPr recycling, avoid development of analgesic tolerance over repeated administration.     

Foraging opportunity: a crucial criterion for horse welfare?

This study aimed at determining the effect of the increase of foraging opportunities on the behaviour and welfare of breeding mares housed in individual boxes but allowed outside 6 h a day in a bare paddock. One hundred Arab breeding mares were divided into two groups of 50 according to the treatment and allowed outside in two bare paddocks at the same density (115 mare/ha) where water and shelter were provided. The treatment consisted in providing the opportunity to forage on hay. Twenty-minute animal focal samplings and scan samplings were used to determine the time budget of the mares during the period from 0900 to 1500 h and study their social behaviour. A total of 300 focal sampling (6000 min), 3300 individual scan sampling (6000 min) and 62 group observations (1240 min) corresponding to the 100 mares were recorded. Non-parametric tests were used to analyse data. Results showed that experimental mares spent more time feeding (65.12% ± 2.40% v. 29.75% ± 2.45%, P < 0.01) and less time in locomotion (11.70% ± 1.31% v. 23.56% ± 1.34%, P < 0.01), stand resting (11.76% ± 2.57% v. 27.52% ± 2.62%, P < 0.01) and alert standing (5.23% ± 1.2% v. 14.71% ± 1.23%, P < 0.01). There was more bonding among experimental mares than control ones (26 v. 14, P < 0.05). Experimental mares showed more positive social interactions (P < 0.01) and less aggression (P < 0.01). These results suggest that giving densely housed mares foraging opportunities improves their welfare.     

A whole mitochondrial genome screening in a MELAS patient: a novel mitochondrial tRNA(Val) mutation

Mitochondrial encephalopathy, lactic acidosis and strokelike episodes (MELAS) syndrome is a mitochondrial disorder characterized by a wide variety of clinical presentations and a multisystemic organ involvement. In this study, we report a Tunisian girl with clinical features of MELAS syndrome who was negative for the common m.3243A>G mutation, but also for the reported mitochondrial DNA (mtDNA) mutations and deletions. Screening of the entire mtDNA genome showed several known mitochondrial variants besides to a novel transition m.1640A>G affecting a wobble adenine in the anticodon stem region of the tRNA(Val). This nucleotide was conserved and it was absent in 150 controls suggesting its pathogenicity. In addition, no mutations were found in the nuclear polymerase gamma-1 gene (POLG1). These results suggest further investigation nuclear genes encoding proteins responsible for stability and structural components of the mtDNA or to the oxidative phosphorylation machinery to explain the phenotypic variability in the studied family.     

Finite element modeling of superelastic nickel–titanium orthodontic wires

Thanks to its good corrosion resistance and biocompatibility, superelastic Ni–Ti wire alloys have been successfully used in orthodontic treatment. Therefore, it is important to quantify and evaluate the level of orthodontic force applied to the bracket and teeth in order to achieve tooth movement. In this study, three dimensional finite element models with a Gibbs-potential-based-formulation and thermodynamic principles were used. The aim was to evaluate the influence of possible intraoral temperature differences on the forces exerted by NiTi orthodontic arch wires with different cross sectional shapes and sizes. The prediction made by this phenomenological model, for superelastic tensile and bending tests, shows good agreement with the experimental data. A bending test is simulated to study the force variation of an orthodontic NiTi arch wire when it loaded up to the deflection of 3 mm, for this task one half of the arch wire and the 3 adjacent brackets were modeled. The results showed that the stress required for the martensite transformation increases with the increase of cross-sectional dimensions and temperature. Associated with this increase in stress, the plateau of this transformation becomes steeper. In addition, the area of the mechanical hysteresis, measured as the difference between the forces of the upper and lower plateau, increases.     

Composition of a molluscan assemblage associated with macrophytes in Menzel Jemil (Bizerte lagoon,SW Mediterranean Sea)

The molluscan species composition and diversity associated with macrophytes was studied throughout 1 year at Menzel Jemil station (Bizerte lagoon, north‐west of Tunisia). A total of 7,539 individuals belonging to 13 species were collected. The molluscan assemblage was mainly composed of gastropods (98.12%, nine species), followed by bivalves (1.88%, four species). Hydrobia acuta ranked first with 49.97% of total abundance, followed by Bittium reticulatum (17.97%), Tritia mutabilis (11.38%), Haminoea navicula (8.98%), Phorcus articulatus (5.17%) and Cerithium vulgatum (3.94%). The large number of juvenile molluscs collected confirms the importance of macroalgae and seagrass for mollusc recruitment. Significant temporal variations of species richness, density and diversity indices of the mollusc assemblage have been observed during the year. Multivariate analyses applied to our data revealed significant relationships between the macrophyte composition and associated molluscan assemblage. The BIOENV analysis indicated that water temperature, phosphates concentration and macrophyte biomass were environmental variables most closely associated with the temporal variation of molluscan assemblage.     

Identification of novel candidate genes by exome sequencing in Tunisian familial male breast cancer patients

Molecular Biology Reports - Male Breast Cancer (MBC) is a rare and aggressive disease that is associated with genetic factors. Mutations in BRCA1&nbsp;and&nbsp;BRCA2&nbsp;account for...     

A note on the time budget and social behaviour of densely housed horses: A case study in Arab breeding mares

We observed a high-density herd (200 mares/ha) of 44 Arab breeding mares, while in a bare paddock in Tunisia. Twenty-minute animal focal samples and scan sampling were used to determine the time budget of the mares during the period from 9 a.m. to 3 p.m. and study their social behaviour. The data obtained reveal restricted behavioural repertoires with missing behaviour like rolling, allogrooming and lying down; unusual time budgets with a high frequency of locomotion that constitutes the most frequent activity (27.9 ± 19.47%) of the mares. Social interactions were restricted to agonistic interactions but despite the high stocking density, aggressions were not that frequent among mares.     

Experimental Change of the Orientation of Two Populations of Talitrus saltator (Crustacea Amphipoda Talitridae) from Cap Bon (North‐Eastern Tunisia)

The orientation of sandhopper populations is adapted to the direction of the shoreline of the sandy beaches where they live; this behaviour was shown to be inherited in some Mediterranean populations. The question was open whether this behaviour could be adaptively modified in case of changing shoreline or passive transfer to a new differently oriented shoreline. The Cap Bon beaches in north‐eastern Tunisia are particularly interesting because they belong to two different Mediterranean Basins, the central and the eastern one, and their supra‐tidal populations do not come together. This work verified the effect of experimental change of the shoreline direction in two populations of Talitrus saltator from Cap Bon (north‐eastern Tunisia) through a displacement experiment. We transferred samples of T. saltator from two different localities (Korba and Ratiba) from their original beach to the familiar one and tested their solar and landscape orientation on the new beach that had an almost opposite direction with respect to the previous one. The comparisons of the results on the home beach and the new one confirmed the use of the solar compass in both populations, as well as the importance of landscape view and optical local sky factor in adjusting the escape direction. In both populations, an increase of scatter was observed on the new beach, especially when individuals could see the landscape. Also, a clear behavioural difference between the two populations was recorded, being Ratiba population not significantly oriented to the shoreline when tested on the unfamiliar beach, while Korba population maintained its home direction also on the new beach.     

Tunisian man‐made wetlands as alternative habitats for waterbirds and their role for conservation

The distribution of wintering waterbirds within some Tunisian artificial wetlands (AW) was studied during the 2004–2007 stable wintering periods. The survey has regarded 88 wetlands including 27 large dams, 25 hill dams and 36 hill lakes. We identified 42,840 individuals representing seven orders, eleven families, 37 species and six functional groups: dabbling ducks, grazing waterfowl, fish‐eaters, deep‐water foragers, shoreline foragers and waders. The population structure analysis showed an absolute dominance of the deep‐water foragers with approximately 82% of observed waterbirds. The total abundance survey showed a fluctuation of population sizes and richness, from thousands to few individuals and from 1 to 25 species, respectively. Analysis results showed that the species distribution is governed by several ecological factors and there was a significant correlation between species abundance and richness and some habitat variables such as area, depth, age, plant cover and hunting disturbance. Investigated AW revealed a significant carrying capacity and refuge serving for the conservation of numerous wintering and endangered waterbird species of high nature conservation value, the White‐headed Duck Oxyura leucocephala that has been observed with relatively high numbers representing more than 40% of the assessed Tunisian–Algerian population.