Impact of deforestation on the abundance,diversity, and richness of Culex mosquitoes in a southwest Cameroon tropical rainforest

Deforestation is a major threat to biodiversity but little data exist on how deforestation in real‐time affects the overall mosquito species community despite its known role in the transmission of diseases. We compared the abundance and diversity of Culex mosquitoes before and after deforestation along a gradient of three different anthropogenic disturbance levels in a tropical rainforest in southwestern Cameroon. The collections were conducted in unlogged forest (January, 2016), selectively logged forest (January, 2017), and within a young palm plantation (October, 2017) using net traps, sweep nets, resting traps, and dipping for immature stages in water bodies. Mosquitoes were morphologically identified to subspecies, groups, and species. A total of 2,556 mosquitoes was collected of which 1,663 (65.06%) belong to the genus Culex, (n=427 (25.68%) in the unlogged forest; n=900 (54.12%) in the selectively logged forest; and n=336 (20.2%) in the young palm plantation) with a significant difference among the habitats. Diversity and richness of mosquitoes varied significantly among habitats with the highest values found in the selectively logged forest (H=2.4; DS=0.87; S=33) and the lowest value in the unlogged forest (H=1.37; DS=0.68; S=13). The results of this study showed that deforestation affects the abundance and diversity of Culex mosquitoes and favors the invasion of anthropophilic mosquitoes. Higher mosquito abundance and diversity in the selectively logged forest than in the pristine forest is notable and some explanations for these differences are discussed.     

The role of Neuropilin-1 in COVID-19

Neuropilin-1 (NRP-1), a member of a family of signaling proteins, was shown to serve as an entry factor and potentiate SARS Coronavirus 2 (SARS-CoV-2) infectivity in vitro. This cell surface receptor with its disseminated expression is important in angiogenesis, tumor progression, viral entry, axonal guidance, and immune function. NRP-1 is implicated in several aspects of a SARS-CoV-2 infection including possible spread through the olfactory bulb and into the central nervous system and increased NRP-1 RNA expression in lungs of severe Coronavirus Disease 2019 (COVID-19). Up-regulation of NRP-1 protein in diabetic kidney cells hint at its importance in a population at risk of severe COVID-19. Involvement of NRP-1 in immune function is compelling, given the role of an exaggerated immune response in disease severity and deaths due to COVID-19. NRP-1 has been suggested to be an immune checkpoint of T cell memory. It is unknown whether involvement and up-regulation of NRP-1 in COVID-19 may translate into disease outcome and long-term consequences, including possible immune dysfunction. It is prudent to further research NRP-1 and its possibility of serving as a therapeutic target in SARS-CoV-2 infections. We anticipate that widespread expression, abundance in the respiratory and olfactory epithelium, and the functionalities of NRP-1 factor into the multiple systemic effects of COVID-19 and challenges we face in management of disease and potential long-term sequelae.     

Liver X Receptor (LXR) activation negatively regulates visfatin expression in macrophages

Adipose tissue macrophages (ATM) are the major source of visfatin, a visceral fat adipokine upregulated during obesity. Also known to play a role in B cell differentiation (pre-B cell colony-enhancing factor (PBEF)) and NAD biosynthesis (nicotinamide phosphoribosyl transferase (NAMPT)), visfatin has been suggested to play a role in inflammation.Liver X Receptor (LXR) and Peroxisome Proliferator-Activated Receptor (PPAR)γ are nuclear receptors expressed in macrophages controlling the inflammatory response. Recently, we reported visfatin as a PPARγ target gene in human macrophages. In this study, we examined whether LXR regulates macrophage visfatin expression. Synthetic LXR ligands decreased visfatin gene expression in a LXR-dependent manner in human and murine macrophages. The decrease of visfatin mRNA was paralleled by a decrease of protein secretion. Consequently, a modest and transient decrease of NAD⁺ concentration was observed. Interestingly, LXR activation decreased the PPARγ-induced visfatin gene and protein secretion in human macrophages.Our results identify visfatin as a gene oppositely regulated by the LXR and PPARγ pathways in human macrophages.     

Human adipose tissue macrophages display activation of cancer-related pathways

Obesity is associated with a significantly increased risk for cancer suggesting that adipose tissue dysfunctions might play a crucial role therein. Macrophages play important roles in adipose tissue as well as in cancers. Here, we studied whether human adipose tissue macrophages (ATM) modulate cancer cell function. Therefore, ATM were isolated and compared with monocyte-derived macrophages (MDM) from the same obese patients. ATM, but not MDM, were found to secrete factors inducing inflammation and lipid accumulation in human T47D and HT-29 cancer cells. Gene expression profile comparison of ATM and MDM revealed overexpression of functional clusters, such as cytokine-cytokine receptor interaction (especially CXC-chemokine) signaling as well as cancer-related pathways, in ATM. Comparison with gene expression profiles of human tumor-associated macrophages showed that ATM, but not MDM resemble tumor-associated macrophages. Indirect co-culture experiments demonstrated that factors secreted by preadipocytes, but not mature adipocytes, confer an ATM-like phenotype to MDM. Finally, the concentrations of ATM-secreted factors related to cancer are elevated in serum of obese subjects. In conclusion, ATM may thus modulate the cancer cell phenotype.     

Quercetin 3-glucoside protects neuroblastoma (SH-SY5Y) cells in vitro against oxidative damage by inducing sterol regulatory element-binding protein-2-mediated cholesterol biosynthesis

The flavonoid quercetin 3-glucoside (Q3G) protected SH-SY5Y, HEK293, and MCF-7 cells against hydrogen peroxide-induced oxidative stress. cDNA microarray studies suggested that Q3G-pretreated cells subjected to oxidative stress up-regulate the expression of genes associated with lipid and cholesterol biosynthesis. Q3G pretreatment elevated both the expression and activation of sterol regulatory element-binding protein-2 (SREBP-2) only in SH-SY5Y cells subjected to oxidative stress. Inhibition of SREBP-2 expression by small interfering RNA or small molecule inhibitors of 2,3-oxidosqualene:lanosterol cyclase or HMG-CoA reductase blocked Q3G-mediated cytoprotection in SH-SY5Y cells. By contrast, Q3G did not protect either HEK293 or MCF-7 cells via this signaling pathway. Moreover, the addition of isopentenyl pyrophosphate rescued SH-SY5Y cells from the inhibitory effect of HMG-CoA reductase inhibition. Last, Q3G pretreatment enhanced the incorporation of [(14)C]acetate into [(14)C]cholesterol in SH-SY5Y cells under oxidative stress. Taken together, these studies suggest a novel mechanism for flavonoid-induced cytoprotection in SH-SY5Y cells involving SREBP-2-mediated sterol synthesis that decreases lipid peroxidation by maintaining membrane integrity in the presence of oxidative stress.     

Distinct membrane compartmentalization and signaling of ephrin-A5 and ephrin-B1

Eph receptor tyrosine kinases and their membrane-bound ligand ephrins form an essential cell communication system. Both ephrin classes have been shown to localize within cell surface lipid rafts, yet regulate different biological processes. In order to provide insight into this distinct behavior, we examined ephrin-A5 and B1 localization and signaling in murine fibroblasts and tissues. Results indicated that ephrin-A5 was constitutively present in detergent-resistant membrane fractions, while ephrin-B1 displayed translocation to membrane fractions upon stimulation. Ephrin-A5 and B1 were present in detergent-resistant membrane fractions with different buoyancies in vitro and in different raft fractions in vivo. Moreover, ephrin-A5 and B1 differentially influenced actin reorganization. Finally, microarray analysis revealed unique patterns of gene expression between the two ephrin classes. We thus demonstrate that distinct localization and compartmentalization provide insight into the subcellular basis for differential signaling observed in ephrin-A and B classes.     

U2 small nuclear RNA localization and expression during bovine preimplantation development.

This study describes the localization of the U2 small nuclear RNA (snRNA) and the major U snRNA group ribonucleoproteins (snRNPs) during bovine preimplantation development. In vitro maturation, fertilization, and oviductal epithelial cell coculture methods were employed to produce several developmental series totalling over 2,000 preimplantation-stage bovine oocytes and embryos. These oocytes and preimplantation embryos were processed for in situ hybridization, immunofluorescence and Northern blotting methods. The U2 snRNA and the major U group snRNPS were localized initially over the germinal vesicle (GV) of preovulatory oocytes but following GV breakdown were released throughout the ooplasm. They subsequently reassociated with both pronuclei during fertilization. From the two-cell to the blastocyst stages, the U2 snRNA and U snRNPs were localized to the interphase nucleus of each blastomere. The levels of U2 snRNA throughout bovine preimplantation development were determined by probing a Northern blot containing total RNA isolated from the following preimplantation bovine embryo stages: one to two cell, eight to 16 cell, early morula (greater than 32 cell), and late morula/early blastocysts. The levels of U2 snRNA remained constant between the one-cell and eight- to 16-cell bovine embryo stages but increased 4.4-fold between the eight- to 16-cell stage and the late morula/early blastocyst stages. The results suggest that a maternal pool of snRNAs is maintained in mammalian preimplantation embryos regardless of the duration of maternal control of development.     

Ephrin A5 expression promotes invasion and transformation of murine fibroblasts

Emerging evidence suggests involvement of the ephrin/Eph receptor system in tumourigenesis. Research on this new role has centred on the contribution of Eph receptors. In contrast, we focused on the elucidation of the role of ephrins, specifically ephrin A5. Results indicated an increase in invasive potential of ephrin A5-expressing murine fibroblasts, which was abolished by addition of a Src family kinase inhibitor. Furthermore, anchorage-independent growth was increased in ephrin A5-expressing cells. Stimulation with EphA5-Fc receptor increased colony size, but not colony number in ephrin A5 transfectants. Moreover, we observed morphogenetic transformation of ephrin A5-expressing 3T3 cells into a branching network when plated onto Matrigel. This behaviour was specific to ephrin A5 transfectants, as 3T3 cells expressing ephrin B1 displayed a phenotype similar to control 3T3 cells. We conclude that ectopic expression of ephrin A5 in murine fibroblasts elevates oncogenic potential, including increased invasive behaviour, anchorage-independent growth, and morphological transformation.