Biogeography of central African forests: Determinants,ongoing threats and conservation priorities of mammal assemblages

Aim

Central Africa shelters diverse and iconic megafauna, which is threatened by climate and land-use changes and increased hunting-induced defaunation. Though crucial for coordinating regional conservation actions, how species assemblages are spatially structured remains poorly understood. This study aims to fill this knowledge gap for mammals across central African forests.

Location

Tropical moist forests from Nigeria to the Albertine Rift.

Methods

An extensive compilation of forest-dwelling mammal species lists was made from wildlife and bushmeat-related surveys across central Africa. A beta-diversity approach enabling the clustering of surveys composed of similar species was implemented to identify and delimit zoogeographic districts, separately for three well-documented mammal orders: carnivores, primates and artiodactyls. Random forest classification models were then used to identify the environmental determinants of the district's distribution and to produce a continuous zoogeographic map (and associated uncertainties) critical to assess the conservation status of each district and their ongoing threats.

Results

While carnivores do not present a clear spatial structure within central African forests, our findings highlight the structuring role of rivers on both primate and artiodactyl assemblages' distributions. We retained eight and six spatially congruent districts for primates and artiodactyls, respectively. These districts were shaped by the Ubangi-Congo River system, and the Cross and Sanaga Rivers, with a secondary role of insularity and precipitation identified for primates. Highly threatened districts were highlighted, especially in Nigeria and in the Democratic Republic of Congo, the latter including vast areas that are understudied and poorly represented in the protected area network.

Main Conclusions

Beyond refining our understanding of the diversity and uniqueness of mammalian assemblages across central African forests, our map of zoogeographic districts has far-reaching implications for the conservation of highly threatened taxa, allowing to target species and areas of interest for further sampling, conservation and rewilding efforts.     

Single molecule analysis indicates stimulation of MUTYH by UV-DDB through enzyme turnover

The oxidative base damage, 8-oxo-7,8-dihydroguanine (8-oxoG) is a highly mutagenic lesion because replicative DNA polymerases insert adenine (A) opposite 8-oxoG. In mammalian cells, the removal of A incorporated across from 8-oxoG is mediated by the glycosylase MUTYH during base excision repair (BER). After A excision, MUTYH binds avidly to the abasic site and is thus product inhibited. We have previously reported that UV-DDB plays a non-canonical role in BER during the removal of 8-oxoG by 8-oxoG glycosylase, OGG1 and presented preliminary data that UV-DDB can also increase MUTYH activity. In this present study we examine the mechanism of how UV-DDB stimulates MUTYH. Bulk kinetic assays show that UV-DDB can stimulate the turnover rate of MUTYH excision of A across from 8-oxoG by 4–5-fold. Electrophoretic mobility shift assays and atomic force microscopy suggest transient complex formation between MUTYH and UV-DDB, which displaces MUTYH from abasic sites. Using single molecule fluorescence analysis of MUTYH bound to abasic sites, we show that UV-DDB interacts directly with MUTYH and increases the mobility and dissociation rate of MUTYH. UV-DDB decreases MUTYH half-life on abasic sites in DNA from 8800 to 590 seconds. Together these data suggest that UV-DDB facilitates productive turnover of MUTYH at abasic sites during 8-oxoG:A repair.     

Porphyromonas gingivalis and Treponema denticola Synergistic Polymicrobial Biofilm Development

Chronic periodontitis has a polymicrobial biofilm aetiology and interactions between key bacterial species are strongly implicated as contributing to disease progression. Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia have all been implicated as playing roles in disease progression. P. gingivalis cell-surface-located protease/adhesins, the gingipains, have been suggested to be involved in its interactions with several other bacterial species. The aims of this study were to determine polymicrobial biofilm formation by P. gingivalis, T. denticola and T. forsythia, as well as the role of P. gingivalis gingipains in biofilm formation by using a gingipain null triple mutant. To determine homotypic and polymicrobial biofilm formation a flow cell system was employed and the biofilms imaged and quantified by fluorescent in situ hybridization using DNA species-specific probes and confocal scanning laser microscopy imaging. Of the three species, only P. gingivalis and T. denticola formed mature, homotypic biofilms, and a strong synergy was observed between P. gingivalis and T. denticola in polymicrobial biofilm formation. This synergy was demonstrated by significant increases in biovolume, average biofilm thickness and maximum biofilm thickness of both species. In addition there was a morphological change of T. denticola in polymicrobial biofilms when compared with homotypic biofilms, suggesting reduced motility in homotypic biofilms. P. gingivalis gingipains were shown to play an essential role in synergistic polymicrobial biofilm formation with T. denticola.     

Isolation of a native osteoblast matrix with a specific affinity for BMP2

During their commitment and differentiation toward the osteoblast lineage, mesenchymal stem cells secrete a unique extracellular matrix (ECM) that contains large quantities of glycosaminoglycans (GAGs). Proteoglycans (PGs) are major structural and functional components of the ECM and are composed of a core protein to which one or more glycosaminoglycan sugar chains (GAGs) attach. The association of BMP2, a member of the TGF-β super-family of growth factors, and a known heparin-binding protein, with GAGs has been implicated as playing a significant role in modulating the growth factor’s in vitro bioactivity. Here we have characterised an osteoblast-derived matrix (MX) obtained from decellularised MC3T3-E1 cell monolayers for its structural attributes, using SEM and histology, and for its functional ability to maintain cell growth and viability. Using a combination of histology and anion exchange chromatography, we first confirmed the retention of GAGs within MX following the decellularisation process. Then the binding specificity of the retained GAG species within the MX for BMP2 was examined using a BMP2-HBP/EGFP (BMP2 Heparin-Binding Peptide/Enhanced Green Fluorescent Protein) fusion protein. The results of this study provide further evidence for a central role of the ECM in the regulation of BMP2 bioactivity, hence on mesenchymal stem cell commitment to the osteoblast lineage.     

Dopamine D3 receptor antagonists: The quest for a potentially selective PET ligand. Part one: Lead identification

The synthesis and SAR of a new series of potent and selective dopamine D₃ receptor antagonists is reported.     

Changes in bird populations on sample lowland English farms in relation to loss of hedgerows and other non-crop habitats

Farmland bird population trends were examined on a sample of lowland English farms to assess the relative importance of habitat loss and habitat degradation. Data were extracted from 11 farms surveyed by territory mapping between 1966 and 1986 as part of the British Trust for Ornithology's Common Birds Census. The population size of 38 bird species was quantified for each farm in each year. The extents of five non-crop habitats were measured at 4-yearly intervals on each farm. The farms were selected because some had undergone extensive removal of non-crop habitats while others had undergone little or none. Although declines were commonest on farms where the severest habitat loss had taken place, we found no evidence that habitat loss was the main factor causing population declines: all 11 farms had significant numbers of declining species, even where habitat loss was minimal. Furthermore, general linear modelling found no significant effects of habitat loss on population trends and principal-components analysis found limited effects of habitat extent on community composition. These results suggest that habitat loss is of secondary importance in causing farmland bird population declines. We suggest that other processes, such as habitat degradation, may have caused a baseline population decline in at least 10 farmland bird species and that declines may have been exacerbated by localised habitat loss. Received: 4 February 1998 / Accepted: 1 April 1998     

Replacing dietary glucose with fructose increases ChREBP activity and SREBP-1 protein in rat liver nucleus

Diets high in fructose cause hypertriglyceridemia and insulin resistance in part due to simultaneous induction of gluconeogenic and lipogenic genes in liver. We investigated the mechanism underlying the unique pattern of gene induction by dietary fructose. Male Sprague-Dawley rats (n = 6 per group) were meal-fed (4 h/d) either 63% (w/w) glucose or 63% fructose diet. After two weeks, animals were killed at the end of the last meal. Nuclear SREBP-1 was 2.2 times higher in fructose-fed rats than glucose-fed rats. Nuclear FoxO1 was elevated 1.7 times in fructose group, but did not reach significance (P = 0.08). Unexpectedly, no difference was observed in nuclear ChREBP between two groups. However, ChREBP DNA binding was 3.9× higher in fructose-fed animals without an increase in xylulose-5-phospate, a proposed ChREBP activator. In conclusion, the gene induction by dietary fructose is likely to be mediated in part by simultaneously increased ChREBP activity, SREBP-1 and possibly FoxO1 protein in nucleus.     

The reverse mode of the Na(+)/Ca(2+) exchanger provides a source of Ca(2+) for store refilling following agonist-induced Ca(2+) mobilization

Agonist-induced contraction of airway smooth muscle (ASM) can be triggered by an elevation in the intracellular Ca(2+) concentration, primarily through the release of Ca(2+) from the sarcoplasmic reticulum (SR). The refilling of the SR is integral for subsequent contractions. It has been suggested that Ca(2+) entry via store-operated cation (SOC) and receptor-operated cation channels may facilitate refilling of the SR. Indeed, depletion of the SR activates substantial inward SOC currents in ASM that are composed of both Ca(2+) and Na(+). Accumulation of Na(+) within the cell may regulate Ca(2+) handling in ASM by forcing the Na(+)/Ca(2+) exchanger (NCX) into the reverse mode, leading to the influx of Ca(2+) from the extracellular domain. Since depletion of the SR activates substantial inward Na(+) current, it is conceivable that the reverse mode of the NCX may contribute to the intracellular Ca(2+) pool from which the SR is refilled. Indeed, successive contractions of bovine ASM, evoked by various agonists (ACh, histamine, 5-HT, caffeine) were significantly reduced upon removal of extracellular Na(+); whereas contractions evoked by KCl were unchanged by Na(+) depletion. Ouabain, a selective inhibitor of the Na(+)/K(+) pump, had no effect on the reductions observed under normal and zero-Na(+) conditions. KB-R7943, a selective inhibitor of the reverse mode of the NCX, significantly reduced successive contractions induced by all agonists without altering KCl responses. Furthermore, KB-R7943 abolished successive caffeine-induced Ca(2+) transients in single ASM cells. Together, these data suggest a role for the reverse mode of the NCX in refilling the SR in ASM following Ca(2+) mobilization.     

Treatment Initiation,Program Attrition and Patient Treatment Outcomes Associated with Scale-Up and Decentralization of HIV Care in Rural Malawi

Objective

To describe patient antiretroviral therapy (cART) outcomes associated with intensive decentralization of services in a rural HIV program in Malawi.

Methods

Longitudinal analysis of data from HIV-infected patients starting cART between August 2001 and December 2008 and of a cross-sectional immunovirological assessment conducted 12 (±2) months after therapy start. One-year mortality, lost to follow-up, and attrition (deaths and lost to follow-up) rates were estimated with exact Poisson 95% confidence intervals (CI) by type of care delivery and year of initiation. Association of virological suppression (<50 copies/mL) and immunological success (CD4 gain ≥100 cells/µL), with type of care was investigated using multiple logistic regression.

Results

During the study period, 4322 cART patients received centralized care and 11,090 decentralized care. At therapy start, patients treated in decentralized health facilities had higher median CD4 count levels (167 vs. 130 cell/µL, P<0.0001) than other patients. Two years after cART start, program attrition was lower in decentralized than centralized facilities (9.9 per 100 person-years, 95% CI: 9.5–10.4 vs. 20.8 per 100 person-years, 95% CI: 19.7–22.0). One year after treatment start, differences in immunological success (adjusted OR = 1.23, 95% CI: 0.83–1.83), and viral suppression (adjusted OR = 0.80, 95% CI: 0.56–1.14) between patients followed at centralized and decentralized facilities were not statistically significant.

Conclusions

In rural Malawi, 1- and 2-year program attrition was lower in decentralized than in centralized health facilities and no statistically significant differences in one-year immunovirological outcomes were observed between the two health care levels. Longer follow-up is needed to confirm these results.