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Les patients SLA et les souris modèles présentent un dysfonctionnement métabolique qui coïncide avec le changement de concentration de différentes espèces lipidiques. Notre hypothèse est qu’un tel dysfonctionnement métabolique au niveau musculaire conduirait aux premiers changements observés dans la SLA. Nous avons montré que l’expression de la stéaroyl-coenzyme A désaturase 1 (SCD1), une enzyme clé de la synthèse des acides gras mono-insaturés à partir des acides gras saturés, est diminuée dans le muscle avant les premiers symptômes moteurs observés chez les souris modèles de SLA. Dans ce modèle murin, les altérations en acides gras au niveau circulant et hépatique, traduisant les changements de SCD1,apparaissent lors des premiers symptômes de la pathologie. De plus, l’inhibition pharmacologique de l’activité de SCD1 mime le phénotype métabolique des souris modèles de SLA. Notre étude a ainsi montré que la diminution de la SCD1 joue un rôle important pour l’activité neuromusculaire. Elle module les besoins énergétiques, maintien l’activité musculaire par augmentation du métabolisme oxydatif et agit sur l’expression de gènes impliqués dans le développement et le fonctionnement de la jonction neuromusculaire. De plus, l’ablation du gène SCD1 stimule la récupération fonctionnelle musculaire après lésion du nerf. L’inhibition pharmacologique de SCD1 apporte également une protection au muscle. Nous avons pu conclure de cette étude qu’une modification de l’expression de SCD1 ainsi que du profil d’acides gras peut apporter une protection au muscle pour lutter contre la pathologie. En outre, des inhibiteurs de l’activité enzymatique de la SCD1 pourraient être développés comme traitement thérapeutique dans la SLA. / ALS patients and mouse model manifest metabolic dysfunctions that coincide with the modified levels of various lipid species. We postulated that metabolic dysfunctions in muscles function as a leading preliminary change in ALS. We have noted that the expression of stearoyl-CoA desaturase 1 (SCD1), a key enzyme that synthesises monounsaturated fatty acids (MUFAs) from saturated fatty acids (SFAs), is diminished even at pre-symptomatic stage in the muscles of an ALS mouse model. In these mice, alterations in circulating and hepatic fatty acid composition, resulting from SCD1 modification, arise at a critical stage of disease onset. Of note, inhibition of SCD1 enzymatic activity by a specific pharmacological agent mimics the metabolicphenotype of the ALS mouse model. Our study also elucidates that the lack of SCD1 plays a vital role in neuromuscular function. It modulates energy supply, and maintains muscle activity by increasing oxidative metabolism and the expression of genes involved in neuromuscular junction development and function. In addition, ablation of SCD1 gene stimulates functional recovery of muscles after a nerve lesion. Pharmacological SCD1 inhibition also provides a protection to muscle function. We conclude that alteration in SCD1 expression and related altered fatty acid profile may protect muscles against pathology. Therefore, SCD1 inhibitors can be developed as a therapeutic intervention.

Budongo Forest Reserve (BFR) is a flagship reserve for primate conservation due to its abundant chimpanzee (Pan troglodytes) population, and its current management policy for multiple economic, conservation and environmental benefits. The identification and better understanding of the structure and dynamics of the forest/plant community types, patterns of species distribution and quantitative properties of their diversity is important to the conservation and sustainable management of tropical rainforests. This study seeks to contribute to a better understanding of the BFR forest community types, species diversity patterns and environmental correlates, as well as natural regeneration processes (i.e. seedling establishment and sprouting). Data on vegetation and environmental variables were collected using rectangular 50 x 100m (0.5 ha) plots, sub-divided into five equal contiguous (20 x 50 m) 0.1 ha sub-plots. Data on land-use/cover changes, and relevant associated socio-economic parameters were collected through the analysis of multi-temporal satellite imagery and field observations, as well as interviews of local households and key informants. The study revealed significant land-use/cover changes, with the area under sugarcane cultivation increasing over 17-fold, from 690 ha in 1988 to 12729 ha in 2002, with a concomitant loss of about 4680 ha (8.2% loss) of forest/woodland, mainly in the southern part of BFR. These changes are attributed to agricultural expansion, a rapidly increasing human population, exacerbated by large influxes of refugees, lack of alternative sources of income, conflicts of interest and political interference in the management of BFR, and an unclear land tenure system. The need for more land for agricultural expansion and the loss of woodlands (a source of building materials and fuelwood for the local communities) is leading to the invasion of and encroachment on BFR, which threatens plant and wild animal conservation. The study revealed that the vegetation of BFR is formed by a mosaic of plant communities, with the major forest types being; Pseudospondias microcarpa Swamp Forest, Funtumia elastica - Pouteria altissima, Lasiodiscus mildbraedi - Khaya anthotheca and Cynometra alexandri - Rinorea ilicifolia forest communities. Canonical correspondence analysis (CCA) indicated that soil nutrients (Si, Ca, N, Fe and Li) and anthropogenic disturbances are the main factors controlling forest community patterns. The variances explained as a proportion of total inertia were relatively high (0.53 and 0.56 for basal area and abundance, respectively), showing how well the measured variables explained species composition. These plant communities differed significantly in terms of woody species diversity and richness; being highest in the Pseudospondias microcarpa swamp and lowest in the Cynometra alexandri-Rinorea ilicifolia forest. However, about 48 species were shared between the forest community types. A total of 269 species representing 171 genera and 51 families was recorded. Fisher’s alpha-diversity ranged 4.45-30.59 and 3.07-29.7 for stem diameters ≥2.0 cm and ≥10 cm, respectively, being significantly higher for stem diameters ≥2.0 cm. The use of stem diameters ≥2.0 cm unveiled 53 more species (19.7%), with only 216 species recorded for the standard ≥10 cm dbh minimum size usually applied in tropical forests. A SHE analysis also showed greater richness (ln(S)) and H diversity for the >2.0 cm than the ≥10cm stem diameters. Hence, the study reaffirmed that the use of 10 cm as a minimum dbh in woody plant diversity studies in forests, where many tree species rarely exceed 10 cm stem diameter, is highly likely to underestimate diversity and richness, potentially biasing the understanding of diversity patterns. The most speciose families were Euphorbiaceae, Fabaceae, Rubiaceae, Moraceae, Meliaceae, Rutaceae, Annonaceae, and Flacourtiaceae, accounting for 147 species. Families with the highest Familial Importance values (FIV) were; Fabaceae (17.5), followed by Euphorbiaceae (16.3), and Ulmaceae (8.35). The BFR exhibits characteristics intermediate between log-normal and log-series species-abundance distributions, indicating a community with a small number of abundant species and a relatively large proportion of rare species. Both Whittaker’s (βw) and the Morisita-Horn Index measures of β-diversity consistently showed higher β-diversity for logged and arboricide treated areas, followed by logged only, and then nature reserve historical management practice types. β-diversity was relatively high at the total forest community scale, but lower for stem diameter ≥2.0 cm than ≥10.0 cm data. Environmental variables significantly explained 66.5% and 61.9% of the variance in species composition for stem diameter ≥2.0 cm and ≥10.0 cm data, respectively. Hence, the variation in species composition of BFR is characterised by significant spatial patterns, and the patterns in β-diversity are to a great extent associated with environmental heterogeneity (i.e. soil nutrients, topographic and light gradients) and anthropogenic disturbances. Investigation of natural regeneration showed that sprouting is generally common among the woody species, with both canopy and sub-canopy trees sprouting prolifically. Of the 122 species affected by ii harvesting, and tree and branch fall disturbances, 199 (97.5%) from 31 families sprouted from the cut stumps, with only Caloncoba crepiniana (De Wild. & Th.Dur.) Gilg exhibiting both stem and root sprouting. Stump basal diameter, height, bark-thickness, and height of stump above the ground at which the first sprout emerged, were significant predictors of sprouting ability among individuals. Number of sprouts/stump differed significantly among families, species, and stump size-classes. Of the 241 seedling species, representing 46 families, about 30.3% were rare (only 2-10 individuals); while 12% were very rare (only 1 individual each). Cynometra alexandri C.H. Wright and Lasiodiscus mildbraedii Engl. were the most abundant seedlings and also among the most widely distributed species in the forest. Analysis of similarity (ANOSIM) revealed significant differences in seedling composition between transects, but not between topographic positions or historical management practice types. Canonical Correspondence Analysis (CCA) showed that the measured environmental variables significantly explained 59.4% of the variance in seedling species distributions, with the three most important variables being organic matter, titanium and leaf area index (LAI; an indicator of light availability below the canopy). Hence, the important mechanisms influencing regeneration via seedlings in BFR operate through the soil system, and the ground and canopy vegetation characteristics. Nine of the 15 intensively studied multiple-use species, namely L. mildbraedii, Celtis Mildbraedii Engl., Pouteria altissima (A. Chiev.) Aubrev. & Pellegr., Chrysophyllum albidum G. Don., C. alexandri, Diospyros abyssinica (Hiern) F. White, Funtumia elastica (Preuss) Stapf., Chrysophyllum perpulchrum Hutch. & Dalz, and Antiaris toxicaria (Pers.) Lesch. had highly negative size-class distribution (SCD) slopes and substantial seedling regeneration. While Alstonia boonei De Wild. and Cordia millenii Bak. had weakly negative SCD slopes and pulsed or sporadic regeneration patterns. The wide distribution of seedlings for a variety of species, and with most of the intensively studied species having population structures showing healthy regeneration patterns, suggests that BFR is currently experiencing a continuous regeneration phase. In conclusion, the gradients in the vegetation of BFR are a reflection not only of site conditions as shown by the edaphic and abiotic factors, but also the history of human interventions.